More Canadian and USA studies confirm that vigorous vitamin D need applies especially to those living in far northern USA-Canada and EurAsia etc; but also to all of us globally who spend little time well exposed to the sun- especially the more driven who both live/work indoors and cover even our limbs and heads outdoors as eg more ‘observant’ adults of many faiths do. As a new Creighton Univ study shows, we are at minimal risk of kidney stones on vigorous supplement vit D3 provided we balance it with enough water and magnesium supplement,

This is why in this age of increasing stress, longevity, epidemics, and pollution of both environment and the food and medicine chains, we have for a couple of years now been advocating and taking vitamin D3 – on a century of voluminous evidence (62500 papers on Pubmed alone) since 1914 from top nutritional scientists like Drs Jack Drummond, Linus Pauling, Walter Stumpf, Chris Nordin, Chris Gallagher, Rob Heaney, John Cannell, Bill Grant, Mike Holick, Cedric Garland, ea – at least vit D3 50 000iu a week (~7000iu/d) ie a million units every 20 weeks; retail costing R30 ie R6pm for us aging frailer types (half that dose ie 50 000iu twice a month @R3/month for the poor/ well or small kids).. at R12/US$, that costs all of $3 to $6 a year.

On about 9000iu vit D3 average supplement/day, my total 25OH vit D bloodlevel runs about 90-100 ng/ml ie 220-250 nmol/l. so only 400- 1000iu vit D /day will boost the vit D bloodlevel and benefits little if not trivially.

But vigorous D3 dose must be buffered by vit K2 about >100mcg/day , magnesium about 400mg/d, and the usual basket of other ~50 vits, minerals and other natural supplements, to protect us from kidney and arterial calcification etc. We have previously highlighted trials eg from Pakistan showing that even 600 000iu vit D3 a month ie ~20 000iu/day safely and greatly improves recovery and healing from severe PTB+- AIDS in eg frail Pakistatin patients; whereas overdose of 90year old patients with a 2million iu vit D3 dose (in Netherlands) produced no toxicity. Hence we load sick patients with (an antibiotic-like ) 200 000 to 400 000iu dose before continuing weekly or fortnightly maintenance- with the sickest fattest getting the highest dose, and infants scaled down accordingly (after a loading dose of eg 25 000iu) to eg 1000-2000iu/d, or 50000iu 1/2 scoop ie 25000iu every 2 weeks- the older extrapolation (as for adults) of ~100iu/kg/day.

For the concerned vegan, vitamin D is vegetarian: supplement of vit D2 is extracted from yeast or mushrooms; vit D3 by UV irradiation of cholesterol from lanolin. Like all life, since vitamin D soltriol is a sun-induced sterol oil product (in this case of cholesterol which in turn is built via vitamin C ascorbic acid from plant glucose-sugar), vitamin D does not contain or be made from animal flesh ie animal protein nitrogen any more than does fish oil.

Vitamin D may keep low-grade cancer from becoming aggressive: http://www.sciencedaily.com/releases/2015/03/150322080155.htmTaking vitamin D supplements could slow or even reverse the progression of less aggressive, or low-grade, prostate tumors without the need for surgery or radiation, scientists say. Taking vigorous vits C & D does this for all cancers, all disease.

A Statistical Error in the Estimation of the Recommended Dietary Allowance for Vitamin D. Letter to Veugelers, P.J. and Ekwaru, J.P., Nutrients. 2015 Mar 10;7(3):1688-90. doi: 10.3390/nu7031688. Nutrients 2014, 6, 4472-4475; doi:10.3390/nu6104472. Heaney , Garland ea. 1Creighton University & University of California, San Diego,GrassrootsHealth, Encinitas, CA . Recently Veugelers and Ekwaru published data indicating that, in its dietary reference intakes for calcium and vitamin D, the Institute of Medicine (IOM) had made a serious calculation underestimation [2]. Using the same data set as had the IOM panel, these investigators showed that the Recommended Dietary Allowance (RDA) for vitamin D had been underestimated by an order of magnitude. Veugelers and Ekwaru, using the IOM’s data, calculated an RDA of 8895 IU per day. They noted that there was some uncertainty in that estimate, inasmuch as this value required an extrapolation from the available data, which did not include individuals receiving daily vitamin D inputs above 2400 IU/day.[…].

The Institute of Medicine (IOM) issues dietary recommendations on the request of the U.S. and Canadian governments. One of these recommendations is the Recommended Dietary Allowance (RDA). The RDA is the nutrient intake considered to be sufficient to meet the requirements of 97.5% of healthy individuals [1]. The RDA for vitamin D is 600 IU per day for individuals 1 to 70 years of age and is assumed to achieve serum 25-hydroxyvitamin D (25(OH)D) levels of 50 nmol/L or more in 97.5% of healthy individuals [1]. Serum 25(OH)D is the established proxy for vitamin D status and levels of 50 nmol/L or more have been shown to benefit bone health and to prevent disease and injury [1].

The IOM based their RDA for vitamin D on an aggregation of 10 supplementation studies that were carried out during winter months and at locations with latitudes above the 50th parallel north to minimize the influence of cutaneous vitamin D synthesis [2,3,4,5,6,7,8,9,10,11]. As several of these 10 studies examined more than one supplementation dose, collectively they provided 32 study averages of serum 25(OH)D levels. These are replicated as the green diamonds in Figure 1. The IOM regressed the 32 study averages against vitamin D intake to yield the dose response relationship of vitamin D intake and serum 25(OH)D (green solid line in Figure 1). The IOM further calculated the lower and upper 95% confidence prediction interval based on the 32 study averages and the standard deviation of these 32 study averages (green dashed lines in Figure 1). On the basis of this, the IOM estimated that 600 IU of vitamin D would achieve an average 25(OH)D level of 63 nmol/L and a lower 95% confidence prediction limit (2.5 percentile) of 56 nmol/L. The latter value was rounded downwards to 50 nmol/L to accommodate uncertainty in the estimation [1]. This data point (600 IU vitamin D, 50 nmol/L) is the basis for the current RDA and for the IOM’s conclusion that an intake of 600 IU of vitamin D per day will achieve serum 25(OH)D levels of 50 nmol/L or more in 97.5% of individuals.

The correct interpretation of the lower prediction limit is that 97.5% of study averages are predicted to have values exceeding this limit. This is essentially different from the IOM’s conclusion that 97.5% of individuals will have values exceeding the lower prediction limit. To illustrate the difference between the former and latter interpretation, we estimated how much vitamin D is needed to achieve that 97.5% of individuals achieve serum 25(OH)D values of 50 nmol/L or more. For this purpose we reviewed each of the 10 studies used by the IOM. Eight studies reported both the average and standard deviation [2,5,6,7,8,9,10,11]. These eight studies had examined a total of 23 supplementation doses [2,5,6,7,8,9,10,11]. For each of these 23 study averages we calculated the 2.5th percentile by subtracting 2 standard deviations from the average (depicted by yellow dots in Figure 2). Next, we regressed these 23 values against vitamin D intake to yield the lower prediction limit (red line in Figure 2). This regression line revealed that 600 IU of vitamin D per day achieves that 97.5% of individuals will have serum 25(OH)D values above 26.8 nmol/L rather than above 50 nmol/L which is currently assumed. It also estimated that 8895 IU of vitamin D per day may be needed to accomplish that 97.5% of individuals achieve serum 25(OH)D values of 50 nmol/L or more. As this dose is far beyond the range of studied doses, caution is warranted when interpreting this estimate. Regardless, the very high estimate illustrates that the dose is well in excess of the current RDA of 600 IU per day and the tolerable upper intake of 4000 IU per day [1].

The public health and clinical implications of the miscalculated RDA for vitamin D are serious. With the current recommendation of 600 IU, bone health objectives and disease and injury prevention targets will not be met. This became apparent in two studies conducted in Canada where, because of the Northern latitude, cutaneous vitamin D synthesis is limited and where diets contribute an estimated 232 IU of vitamin D per day [12]. One study estimated that despite Vitamin D supplementation with 400 IU or more (including dietary intake that is a total intake of 632 IU or more) 10% of participants had values of less than 50 nmol/L [13]. The second study reported serum 25(OH)D levels of less than 50 nmol/L for 15% of participants who reported supplementation with vitamin D [14]. If the RDA had been adequate, these percentages should not have exceeded 2.5%. Herewith these studies show that the current public health target is not being met. We recommend that the RDA for vitamin D be reconsidered to allow for appropriate public health and clinical decision-making.

update 1 March 2015: Screening for Vitamin D Deficiency: Is the Goal Disease Prevention or Full Nutrient Repletion?

Since its founding, the USPSTF has sought to provide a firm evidential base for early detection strategies, evaluating such screening methods as mammography and prostate-specific antigen testing. Although it has also evaluated a few interventions, its predominant focus has been testing for markers that identify persons at risk who are likely to benefit from preventive action. Only recently has the USPSTF ventured into the field—or perhaps the minefield—of nutrition, a territory distant from screening tests and risk assessment, with different and unfamiliar landmarks.

The USPSTF presents its conclusions on testing for vitamin D deficiency (1), reporting that it was unable to find evidence for or against such testing. It noted that one of the likely reasons was the absence of a scientific consensus on both the level of vitamin D status that should be judged “deficient” and what the measurable manifestations of deficiency might be. These are also issues for many other nutrients, such as folate, ascorbate, calcium, and protein. Vitamin D may have seemed to offer a way out of this confusion because serum 25-hydroxyvitamin D [25-(OH)D] concentration is generally recognized as one of the best indices of status for any of a broad array of nutrients. Also, it is now readily measurable and widely utilized.

One of the reasons its promise has not been realized is that most studies of vitamin D efficacy have used a disease-avoidance model, which is the standard approach used by the Institute of Medicine (IOM) for most nutrients (2). Furthermore, disease prevention is the explicit focus of the USPSTF. Nevertheless, the IOM and USPSTF approaches effectively equate health with the absence of disease, an equivalence that nutritionists have long rejected. Instead, nutritionists focus on full nutrient repletion when possible. The inevitable gap between disease prevention and nutrient repletion is still largely unexplored territory. For many nutrients, it can be surprisingly wide, as suggested in this case by studies of the intake required to provide vitamin D in human breast milk in quantities sufficient to meet the needs of infants (3). The IOM’s adult requirement for vitamin D is 600 IU/d (4), which is judged to be sufficient to protect against osteoporotic fracture. In contrast, quantitative and empirical evidence indicates that vitamin D intake from breastfeeding needs to be approximately 6000 IU/d (3, 5). Although high compared with the adult recommendation, such an intake almost exactly reproduces the measured vitamin D status of contemporary Africans leading ancestral lifestyles (6). Such populations provide perhaps our best window on vitamin D levels prevailing during the millennia over which human physiology was adapted to its environment by natural selection.

Whatever the actual requirement or 25-(OH)D cutoff may be, there is another likely reason that the evidence is unclear. The USPSTF drew from systematic reviews and meta-analyses of studies of vitamin D effects, such as the one accompanying the current report (7). In general, the criteria for including studies in such reviews are methodological rather than biological. Of the 6 published biological criteria (8) for including published reports in meta-analyses, the review published in this issue met only 2 (comparable basal status and same chemical form), and several of its component studies met none. Including studies that could never have been informative in the first place (especially when they are large) inevitably biases any review toward the null.

What seems not to have been widely appreciated is that vitamin D exhibits flat response regions at both low and high values of vitamin D status, with a sharp rise in the approximate center of the physiologic range of 25-(OH)D values (8). Studies like the WHI (Women’s Health Initiative), which enrolled women with low vitamin D status values and used a vitamin D dose insufficient to move them into the response range, provide little useful information about vitamin D efficacy. Yet, precisely such studies were included in the review by LeBlanc and colleagues (7). This is not to criticize the WHI, which was designed more than 20 years ago (before vitamin D pharmacology was well-understood), but it is to criticize contemporary reviews and meta-analyses that fail to take advantage of newer information or to use critical biological criteria (8) for selection of studies for analysis of biological effects.

In addition, a disease-avoidance approach becomes problematic for micronutrients in general (and vitamin D in particular) when one understands that micronutrients do not actually cause any of the effects simplistically attributed to them. Although necessary for cell response, such micronutrients by themselves do not initiate or cause the response concerned. For example, vitamin D is a component of the biochemical apparatus that opens the genome to allow access to DNA information needed for a particular cell or tissue response. In terms of cell function, this dependence means that when supplies of the micronutrient are inadequate, cellular response is blunted. This is dysfunction, but not clinically manifest disease. Such dysfunction may indeed lead ultimately to various diseases, but disease prevention remains a dull tool for discerning the defect, and a disease-prevention approach clearly does not measure whether the organism has enough of the nutrient to enable appropriate physiologic responses, such as lactation.

Finally, and aside from the USPSTF’s findings, one must ask whether treating without first testing is sound practice. Certainly, it would be rational to do so if the condition being treated is prevalent and the treatment is safe and inexpensive. That is the case with another micronutrient, iodine, and the iodination of salt. However, the current situation is different because consuming sufficient iodine generally does not require conscious adherence to a particular regimen, whereas taking vitamin D does. Usually, testing improves patient adherence because it provides patient-specific, personally applicable information. General assurances that one probably needs extra vitamin D are not as compelling a motivator as knowing one’s number. Thus, whether the practitioner adheres to the widely divergent guidelines of the IOM (4), the Endocrine Society (9), or the American Geriatrics Society (10), measuring vitamin D status seems to be warranted, not so much to diagnose deficiency but to determine patient status relative to the selected guideline.

update 12 Jan 2015 As the poet Juvenal (died 130AD) wrote: Mens sana in sano corporis– a healthy mind in a healthy body. Its great how the prime antistress homeostatic hormones- a pinch of natural melatonin at night, with ENOUGH daytime anabolic soltriol calciferol vitamin D3, restores good sleep, orchestrate homeostasis of all other hormones especially of the crucial adrenals and gonadals and thus thyroid hormones. ..

Thanks to global human (mostly male) greed enslaving the masses the past 7 millennia ie since at least Sumerian times, we have moved rapidly in our lifetime post WW2 from global homeostatic (food, commodities) plenty to a world of dyshomeostasis- cacostasis stress chaos – in most countries from Afghanistan to Zimbabwe. Just a few years ago South Africa led Africa in productivity and skills, and still has the biggest reserves of riches- minerals- in the world; with boundless natural power (sun, sea) and manpower to drive industry and food production. But in 20 years post apartheid, the ruling ANC under Mbeki and the Zumas has with selfserving treasonous greed brought South Africa to its knees with cacostasis, destruction of continuous water, electricity ; school education, organized and quality food provision ie agriculture, social security, the post office, the national airline, health services, Home Affairs and pensions). Now there are rapidly increasing functionally illiterate or old 16 million on state grants supported by the 6 million capable of meaningfully working and paying taxes if they dont emigrate. And state grants have now been extended to age 23yrs because state school leavers are practically unskilled for anything but being labourers. .

The national powergrid and oil reserves have been degraded so that total indefinite blackouts are now imminent, never mind weekly “outages” crippling work- the economy – and destroying appliances. Never mind increasingly pandemic influenza and HIV, antibiotic resistance puts us in the post-antibiotic era in this age of deadly resistant TB and STDs, with reckless immoral leaders like Zuma and Vavi leading the mob in extramarital sex and provoked violence. .

So as never before, everyone from conception to grave needs realistic regular vitamin D3 supplement at about R3 a month to bolster mental and physical health of children, mothers and the working , never mind the ailing aging, to reduce illhealth costs. . Stress- through raised thyroid, sympathetic and cortisol levels and depressed gastrointestinal, cardiovascular, musculoskeletal and immune control, grossly disrupts homeostasis and shifts victims into catabolic estrogen-dominance , insulin resistance mode- which only the hormone supplements D3 and melatonin, and the essential vitamins and minerals if not risk-laden androgenics can try to balance,

George Chrousos ea. University Athens, Greece since Nat Rev Endocrinol.2009 and now Neuroimmunomodulation. 2015 write: Stress – glucocorticoids – and disorders of the stress system- cacostasis vs homeostasis. All organisms must maintain complex dynamic equilibrium- homeostasis- which is constantly challenged by internal or external adverse forces – stressors. Stress occurs when homeostasis is threatened or perceived; homeostasis is re-established by various physiological and behavioral adaptive responses. Neuroendocrine hormones have major roles in the regulation of both basal homeostasis and responses to threats, and are involved in the pathogenesis of diseases characterized by cacostasis – dyshomeostasis. The stress response is mediated by the stress system, partly located in the central nervous system and partly in peripheral organs. The central, greatly interconnected effectors of this system include the hypothalamic-pituitary-adrenal (HPA) axis and hormones arginine vasopressin, corticotropin-releasing hormone and autonomic norepinephrine centers in the brainstem. Optimal basal activity and responsiveness of the stress system is essential for a sense of well-being, successful performance of tasks, and appropriate social interactions. By contrast, excessive or inadequate basal activity and responsiveness of this system might impair development, growth and body composition, and lead to a host of behavioral and somatic pathological conditions.. Glucocorticoids, the end-products of the HPA axis, play a fundamental role in the maintenance of both resting and stress-related homeostasis and, undoubtedly, influence the physiologic adaptive reaction of the organism against stressors. If the stress response is dysregulated in terms of magnitude and/or duration, homeostasis is turned into cacostasis with adverse effects on many vital physiologic functions, such as growth, development, metabolism, circulation, reproduction, immune response, cognition and behavior. A strong and/or long-lasting stressor may precipitate and/or cause many acute and chronic diseases. Moreover, stressors during pre-natal, post-natal or pubertal life may have a critical impact on our expressed genome.

VITAMIN D ECONOMY & GOAL OF SCREENING: Heaney andArmas, Creighton University QUANTIFYING THE VITAMIN D ECONOMY: Nutrition Reviews Dec 2014; and Screening for Vitamin D Deficiency: Is the Goal Disease Prevention or Full Nutrient Repletion? Ann Intern Med.Nov 2014 write:sunlight and food contribute only modestly to the relevant optimal total serum vit D and 25OHvit D levels: unsupplemented individuals who average blood 25OHvit D of 20 ng/mL are receiving about 2,000 IU/day from nonsupplement sources (i.e food and sun) – whites double the amount compared to dark blacks from skin. . It has been established for 30 years that in fair-skinned individuals, a single exposure to UV-B at one whole-body minimum erythema dose can produce a rise in serum 25D that is equivalent to an oral dose of D3 in the range of 10,000 to 25,000 IU, ie by as little as 10–15 min of whole-body exposure at mid-day in mid-summer in a pale-skinned individual. Pale-skinned northern Europeans show a rise in serum 25D of 9 ng/mL (23 nmol/L) at the end of 4 weeks of exposure. By contrast, in dark-skinned individuals, the rise was half ie 4.5 ng/mL . Meat eaters exhibit higher human 25D status . Input gaps left after estimating solar inputs (on the order of 1,300–1,600 IU/day, as noted above) could well be filled by hitherto unrecognized food sources. For example, Taylor et al.21 report a combined (D3 plus 25D) content of 112 IU vitamin D equivalents for 200 g of beef tenderloin or an egg, associated with 2 ng/mL greater level of serum 25D. The Grassroots Health project collects data on supplement type and has found no difference in the 25D concentration achieved with either 5,000 or 10,000 IU daily doses, irrespective of whether the D3 was delivered via a gel cap in oil or as dry powder in a tablet (unpublished data; S. McDonnell, personal communication). vitamin D could be absorbed from orange juice. On the other hand, fat malabsorption syndromes are known to lead to vitamin D deficiency, and the mechanism is generally considered to be a specific impairment in the absorption of fat-soluble vitamin D. However, poor absorption may reflect not so much mucosal dysfunction, as simple sweeping of any fat-soluble compound out of the gut, dissolved in the unabsorbed fat. Dawson-Hughes et al.,35 using pharmacokinetic methods in individuals with normal absorptive function, reported equal absorbability for D3 under fasting and high-fat meal conditions, with slightly better absorption from a low-fat meal. Mulligan and Licata,36 in an observational study of 17 poor responders to oral D preparations, reported greater absorption from a large meal containing fat than from intake on an empty stomach. However, the limited data, taken as a whole, suggest that the effects of dosage form or vehicle are probably small.

Finally, the issue of D2 versus D3 needs brief mention. Formerly considered controversial, there now seems to be a growing consensus37 that, for equimolar quantities, orally administered D3 raises serum 25D by about twice as much as D2.38–42 This has been shown for bolus doses, short-term continuous administration (12 weeks), and long-term continuous administration (12 months).

Intestinal absorption of D3 is mainly from the jejunum and ileum. Absorbed vitamin D can be found in both the portal venous blood and the lymph that drains the small intestine. The lymphatic pathway may have particular physiological significance for orally acquired vitamin D, since it avoids a first pass of the absorbed vitamin D through the liver. This suggests that the quantitative relationship between vitamin D and 25D will be the same regardless of whether vitamin D enters from the skin or the gut.

Diffusion from the skin into the blood is slow, with a half-time of about 3 days.7 This half-time means that when regular sun exposure is the principal source of D3, serum D3 concentration will be essentially constant.

it is reasonably certain that the concentration of vitamin D in fat tissue is substantially higher than the concentration in serum. – a given volume of fat tissue contains approximately 12 times as much vitamin D as the same volume of serum. However, a several-fold gradient is not surprising as D3 solubility in fat is effectively limitless, while DBP capacity, which is large, is finite.

Assuming a diffusional mechanism and a total body fat mass of 35% of body weight, total body stores in an individual weighing 70 kg would range from 900 to 2,800 µg (37,000 to 113,700 IU). Using the calculations set forth in the prior section and applying them to an individual with a serum 25D level of 20 ng/mL, whose metabolic consumption would be ∼2,000 IU vitamin D/day, the total amount in the reservoir would provide enough of a reserve for 18–57 days at that same rate of utilization. At a serum 25D level of 40 ng/mL, that same reserve would support consumption for only 9–28 days. Neither estimate comes close to compensating for the “vitamin D winter” of most temperate latitudes. The smallness of this reserve explains why even outdoor summer workers who had high daytime skin exposure experienced reductions in 25D averaging approximately 20 ng/mL (50 nmol/L) by late winter. Of note, their 25D values had reached >50 ng/mL (125 nmol/L) by late summer, which is roughly the same as that reported for East Africans living ancestral lifestyles.48 This study indicates both that existing stores at the end of summer were not adequate to maintain the achieved summer level and that the late winter level (∼30 ng/mL) represented a utilization of approximately 3,000 IU/day.

Chemical partition Extracellular 25(OH)D The first step in the chemical conversion of D3 is 25-hydroxylation.Bikle et al.51 showed that skin cells contain all the requisite enzymatic apparatus to produce both 25D and 1,25D. However, it is doubtful that under ordinary circumstances, skin is a major source of the extracellular 25D measured in serum (D. Bikle, personal communication). Other sources remain to be identified.

The efficiency with which D3 is converted to 25D varies widely from individual to individual. Various reasons can be put forth for these inter-individual differences that, though studied in somewhat less detail, have been reported by many investigators. One example is the variable methylation of the CYP2R1 gene and, hence, variable expression of the hepatic 25-hydroxylase.53 While there is currently no final answer, it is clear that differences in intestinal absorption of D3 could not explain the slow rise in participant B, relative to participant A. Moreover, the internal consistency in the shape of the respective curves virtually excludes methodological variability as a cause of the difference.

Extracellular 1,25(OH)2D The second hydroxylation, which produces extracellular 1,25D, occurs predominantly in the proximal convoluted tubular cells of the kidney. While 25-hydroxylation is not highly regulated, the opposite is true for 1,25D, the synthesis of which is upregulated by parathyroid hormone and low serum inorganic phosphorus concentration and downregulated by fibroblast growth factor-23. Note that 1,25D is a principal regulator of intestinal absorption of calcium; during this process, it acts by upregulating expression of the calcium transport apparatus of the enterocyte. This is an endocrine effect as it is mediated through serum endocrine-like activity and exhibits a typical negative feedback control loop. Under usual conditions, 1,25D is necessary for regulation of calcium absorption. However, it is not the only factor involved in this process. It should also be noted that in the absence of other vitamin D metabolites, 1,25D by itself has been reported not to be sufficient to elevate intestinal calcium absorption.55,56

As would be expected for regulator molecules, the serum half-time of 1,25D is short (hours). Its concentration in serum is a reflection mainly of relative calcium need—being high in individuals on low-calcium diets or in those with calcium malabsorption and low in individuals with high calcium intakes. Also, 1,25D has long been recognized to be calcemic when used therapeutically. The mechanism is generally attributed to intestinal calcium absorption, but this cannot be a satisfactory explanation, as increased metabolic input alone (i.e., without considering output) is rarely sufficient to elevate the serum concentration of any metabolite. Moreover, 1,25D and its analogs do not elevate calcium absorption in patients with end-stage renal disease,57 a condition in which the calcemic effect of 1,25D is often readily apparent. While not adequately explored, there remains another possibility, i.e., an effect of 1,25D on bone-lining cells, where a fall in bone fluid pH to just below 7.0 is enough to solubilize bone mineral sufficiently to elevate serum calcium.58 Physical partition

The distinction between the endocrine and the autocrine pathways is one aspect of the physical partition between extracellular and intracellular processing of the vitamin. The prevailing assumption seems to be that most or all of the D3 entering the body is 25-hydroxylated and that the resulting 25D circulates in the blood, where it serves as the substrate for both renal and extrarenal 1 -α-hydroxylation, with the renal 1,25D product circulating in the blood like 25D and with the extrarenal 1,25D never being expressed in the only accessible body compartment, i.e., the blood.

As Hollis and Wagner59 have pointed out, D3 enters cells more readily than does 25D and, as noted above, there are several enzymes other than the hepatic CYP2R1 that are capable of 25-hydroxylation of D3.49,50 Hence, a physical partition of the vitamin D pathways prior to the 25-hydroxylation step has to be given serious consideration. That this is more than just a theoretical possibility is suggested by the fact, noted earlier, that oral 25D elevates serum 25D to a substantially greater extent than does oral D3.28–30 This was shown first by Barger-Lux et al.28 in a 10-week dosing study involving the two molecules. Figure 9 plots the 25D response to the two agents observed in a group of 54 healthy adults and shows a clear divergence of the dose response curves, with a greater than seven-fold difference in slopes. Cashman et al.,30 using a different design, found an approximate five-fold difference in response after 10 weeks of dosing, and Bischoff-Ferrari et al.,29 an approximate four-fold difference after 17 weeks of dosing.

Figure 9 Change in serum 25D plotted as a function of intake for varying oral doses of 25D and D3. Data from Barger-Lux et al.28 That there should be a greater rise in 25D when oral 25D is the source is, in a sense, trivial, as oral 25D is immediately reflected in the serum, while oral vitamin D must first be 25-hydroxylated, a process that, as described above, is necessarily slower, sometimes substantially so. Only a proper pharmacokinetic study that compares area-under-the-curve values for the two agents can fully quantify this difference. Such a study must either be long enough to allow the 25D plateau to be reached while on continuous dosing of D343 or, if using a bolus dose design, must follow the time course for the two agents for probably 4 months so as to allow full 25-hydroxylation of the administered D3 and full consumption of the administered 25D. No such data are currently available, and this aspect of the physical partition must remain speculative. Nevertheless, the issue is an important one, not just for the therapeutics of 25D but also for a full understanding of the vitamin D economy (see below).

The 25D half-time (as measured by Clements et al.60–62 using tracer-labeled 25D) presents certain puzzling features in its own right. A half-time of, say, 20 days (toward the lower end of the range found by Clements et al.) translates to a daily turnover of about 3.47% of the total mass of extracellular 25D. If the size of daily utilization is known, it is possible to calculate the size of the 25D mass from that fractional utilization rate. If all of the vitamin D input to the body is converted to extracellular 25D, then at a serum 25D concentration of 20 ng/mL (requiring, as shown above, a daily input of ∼50 µg), that 50-µg input is numerically equal to the daily turnover. So, total 25D mass would be 50/0.0347, or close to 1,500 µg. This figure is larger by an order of magnitude than that of the measurable total serum content of 25D, and the discrepancy becomes even larger at higher serum 25D concentrations or longer half-times. This seeming discrepancy has not been noted previously, with one potential reason being the computational difficulty of harmonizing biological units (IU), first with mass concentrations (µg/mL), then with SI units (nmol). However, if a substantial fraction of daily input of D3 is 25-hydroxylated intracellularly, after which it is immediately activated to 1,25D, then only the 25D in the extracellular compartment would be labeled by a tracer-based approach to kinetic analysis, and the calculated daily utilization of the circulating 25D would be lower and the corresponding 25D mass estimate would be closer to what is known from blood and soft tissue content. These calculations provide support for the suggestion of Hollis and Wagner59 that “parent compound D” has more functional significance than has usually been thought.

There is one quantitative aspect of the physical partition, whether occurring prior to or after the 25-hydroxylation step, which seems inescapable. Whether one takes as optimal a serum 25D concentration of 20 ng/mL or 40 ng/mL, the molar equivalent D3 inputs required to sustain either level are far higher than the moles of 1,25D required to support the calcium economy. As noted above, a serum 25D of 40 ng/mL requires approximately 4,000 IU/day, or 100 µg/day, and a serum 25D of 20 ng/mL requires approximately 2,000 IU/day, or 50 µg/day. By contrast, the calcium economy requires between 0.5 µg and 2.0 µg of 1,25D/day. (Higher doses, as noted above, produce hypercalcemia.) It follows that >90% of D3 utilization is occurring along the intracellular/autocrine pathway. If that is not the case, then most of the D3 input to the body is degraded metabolically and not used at all. The latter possibility seems quite improbable, particularly in view of the marginal or subadequate vitamin D status that seems nearly universal. Answering this question of the relative potency of oral D3 and 25D will illuminate the partition of D3 between the extracellular and intracellular pathways and will be an important step in unraveling the puzzle of the physical partition.

One instance in which the pre-25D intracellular pathway is operative is the transfer of vitamin D activity into human breast milk.59,63 25D does not transfer across the secretory mucosa of the mammary gland with sufficient efficiency to produce enough vitamin D activity in milk to nourish the infant, while D3 does. However, for this to occur, D3 must be present in the blood that bathes the mammary secretory apparatus. In earlier work, Hollis et al.63 showed that the concentration of vitamin D in human milk was about 28% of the concentration of D3 in maternal blood. In subsequent work (B. Hollis, personal communication), that figure was shown to be closer to 32%, and a recent study by Oberhelman et al.64 showed a transfer fraction that can be calculated to be about 44%. Based on recommendations of both the American Academy of Pediatrics and the Institute of Medicine for infant intake (400 IU vitamin D/day, which requires a milk concentration of about 520 IU/L, i.e., ∼34 nmol/L), these transfer fractions would require a maternal serum vitamin D concentration of about 30–40 ng/mL (78–120 nmol/L). (The corresponding 25D concentration would be >50 ng/mL [125 nmol/L]; see Figure 8.) Hollis and Wagner59 estimate that the total input of D3 needed to maintain a milk concentration sufficient to meet the infant’s needs for vitamin D was approximately 6,000 IU/day. The equivalence value derived above produces a needed input of approximately 6,000 IU/day, which is essentially identical to the empirical estimate of Hollis and Wagner. Dosing schedules and serum D3 concentrations

Dosing frequency for oral vitamin D supplementation regimens will affect serum concentration of D3 in predictable and often very striking ways. This fact has been largely overlooked to date, as the serum concentration of D3 has been generally considered to be of no particular interest in its own right. The rationale for infrequent (or bolus) dosing is that it leads to better adherence and that an excess amount ingested today will be stored in fat for use tomorrow. However, this assumption overlooks the effect of infrequent dosing regimens on D3 blood concentrations.

Serum D3 has a half-time variously estimated to be in the range of 0.5–3.5 days, with most investigators favoring a value of about 1.0 days. In contrast, D3 produced in skin moves into the blood with a half-time of about 3 days. This means that when skin synthesis is the principal source of D3, serum D3 concentration will be essentially constant around the clock, as D3 input to the blood from the skin (though produced mainly at mid-day) is effectively constant. With oral ingestion, intestinal absorptive input of D3 occurs mainly during a 4-h period following ingestion. (In one study, a TMAX of as much as 12 h was reported.65 As this is well beyond the usual mouth-to-cecum transit time, the 12-h figure, if confirmed, would suggest appreciable colonic absorption, or small bowel mucosal retention, or a delay pool in the intestinal lymphatics.) In any case, assuming a 1.0-day half-time, serum D3 concentration will inevitably follow a sawtooth pattern, particularly if oral ingestion is the principal input. Figure 10 displays the patterns for purely cutaneous input and for daily, weekly, and biweekly oral administration. With a once-a-week schedule, as is evident from Figure 10, serum D3 concentrations are close to zero for several days each week and below the reference level for most of the interdose interval. Thus, in the practical order, a nursing woman who takes her total weekly dose of vitamin D once each week would produce milk with little or no D content for roughly 4 of the 7 days in each week. This irregular delivery will be even more pronounced with biweekly or less frequent dosing schedules.

Figure 10 Calculated time courses for serum D3 concentration for varying oral dosing intervals. The reference level is the serum concentration for continuous (as contrasted with intermittent) dosing. Each dosing scheme provides the same cumulative intake, according to one of the following regimens: once daily, or 7 times the daily intake once weekly, or 14 times the daily intake once every 2 weeks. It should be stressed that Figure 10 illustrates the concept and is not a depiction of actually measured serum concentrations of D3. Under input conditions in excess of daily use, unused D3 will accumulate in fat, and its concentration there would be predicted to damp the oscillations of D3 concentration in serum to some extent.

An additional feature of interval dosing is the high D3 concentration peaks achieved in the days following each dose. The impact of such high D3 levels is unclear, although Vieth66 has pointed to the induction of the 24-hydroxylation pathway as a likely consequence, with a corresponding reduction in effective vitamin D activity. Further, as the binding capacity of DBP is approximately 4.7 µmol67 (or ∼78,000 IU/L), with true Stosstherapie, as in several recent studies,68,69 the DBP will be fully saturated by the ingested D3, resulting in displacement of both 1,25D and 25D off DBP and into circulation as free or unbound moieties for several days after dosing (i.e., until fat uptake lowers serum D3 sufficiently). This effect amounts to a transient vitamin D intoxication of uncertain physiological import. Unfortunately, there is essentially no published information about vitamin D concentrations in the immediate post-dosing period following large bolus doses. Whatever else may be said of Stosstherapie, it certainly is not physiological. Factors influencing serum 25D concentration

Aside from the possible importance of D3 concentration as the substrate for autocrine activity of vitamin D, there is general agreement that serum 25D concentration is currently the principal indicator of vitamin D status.70 This is because extrarenal conversion of 25D to 1,25D operates at concentrations below the kM for the tissue 1 -α-hydroxylases; hence, serum 25D concentration limits the amount of 1,25D a tissue can synthesize when its cells are stimulated to produce a vitamin D-dependent response. While there is no consensus as to the optimal serum 25D concentration, there is also no disagreement about the importance of the substrate, regardless of which concentration may be deemed optimal.

Input of D3, a factor that manifestly affects 25D concentration, has been the subject of much of the previous discussion. Attention is now focused on the effect on serum concentration of 25D produced by variations in body size and in D3 output, i.e., utilization and/or degradation of the 25D in serum. Obesity

One widely recognized influence on 25D concentration is obesity, with serum 25D being lower in obese individuals. This was originally attributed to a phenomenon termed “sequestration” (implying trapping of vitamin D in adipose tissue of obese individuals).71 However, Drincic et al.72 have shown that simple volumetric dilution is both a more logical explanation and one that fully explains the weight-based difference. Curiously, body mass index works in various regression models almost as well as body weight (and somewhat better in some datasets). This is surprising as body mass index is not a measure of mass but of fatness. The reason is presently unclear, and this observation suggests the possible existence of further mechanisms operating in obese individuals. Parathyroid hormone-1,25D axis Clements et al.60–62 showed that 25D half-time in serum ranged from 15 to >35 days, with 25D half-time being inversely related to parathyroid hormone concentration. The parathyroid hormone effect, noted both in patients with hyperparathyroidism and in animals subjected to calcium deprivation, was, in turn, mediated by serum 1,25D concentration. Why 25D utilization (or degradation) should rise in the face of calcium need is physiologically unclear, particularly as renal 1,25D synthesis is not as dependent on 25D concentration as the autocrine functions of vitamin D.

Inflammation. The other major influence on serum 25D concentration is inflammation. It has been reported that vitamin D status is reduced in the face of systemic inflammatory processes.73–78 For example, Duncan et al.75 reported an inverse correlation of 25D with serum C-reactive protein, with 25D being 40% lower as serum C-reactive protein rose from <5 mg/L to >80 mg/L. Autier et al.,79 in a metaanalysis of the several reports on this relationship, confirmed the existence of the association but attributed the reduced vitamin D status to underlying illness rather than to the inflammation itself. That conclusion may be partly correct, at least for some chronic illnesses, but it cannot apply to the many documented cases in which vitamin D status drops acutely across an inflammatory episode, as with total knee arthroplasty.73,77 In one case study, Henriksen et al.73 reported a 12% drop in 25D by day 2 after total knee arthroplasty and a nearly 80% drop by post-surgery week 8. Reid et al.77 evaluated a series of 33 patients who underwent total knee arthroplasty and reported an approximate 40% drop in total 25D and a 33% drop in calculated free 25D by day 2 after surgery, which was associated with large increases in C-reactive protein.

Decreases in 25D of this magnitude and rapidity cannot be explained by decreased synthesis and must, therefore, reflect increased utilization, degradation, or loss. Depending on which values may be estimated for the total 25D mass (see above), reductions in 25D concentration of the size reported by Reid et al. translate to a loss of several hundred micrograms from the body, which is substantially greater than ordinary daily utilization of vitamin D. While increased utilization cannot be ruled out, it seems unlikely to be the sole explanation. Another possibility, which was suggested by Waldron et al.,76 is the loss of DBP (with its bound ligand) in the urine. In 30 patients undergoing elective orthopedic surgery, the ratio of DBP to creatinine in urine rose 2.5× by the second day post-surgery; this was associated with a >20-fold increase in C-reactive protein. Renal loss could certainly explain much or all of the change in 25D observed in these studies and could be the result of interference with the kidney’s megalin–cubilin system, possibly produced by the anesthesia or inflammatory cytokines associated with the surgery.

Although not directly related to the major focus of this review, the conclusion reached by several of the authors of the studies just reviewed, i.e., that, while inflammation clearly reduced D status, this reduction was without nutritional significance, is in no way supported by data in any of the papers concerned, nor is it consistent with the importance of serum 25D concentration as the principal limiting factor in the autocrine pathway.

METABOLISM AND UTILIZATION the data assembled here make clear that, even with today’s widespread vitamin D inadequacy, total vitamin D inputs are far higher than previously thought, food sources are greater than previously recognized, and solar input, though theoretically capable of fully meeting any plausible vitamin D requirement, is actually only a minor present-day contributor to total vitamin D input at the population level. That does not mean that the human requirement is more easily met. Rather, it indicates that the requirement is higher than previously recognized, with populations still short of meeting that requirement by the amount needed to move prevailing serum 25D concentrations from current values to putatively healthier levels.

These analyses also make clear that at prevailing inputs (i.e., <4,000 IU/day), D3 is rapidly 25-hydroxylated and little D3 circulates in the blood or is shunted into adipose tissue for storage. Additionally, the recent recognition that oral 25D may raise serum 25D to a significantly greater extent than does oral vitamin D suggests the possibility of a hitherto little recognized or explored intracellular pathway in which the entire metabolic sequence is handled within certain target tissues and is not reflected in blood. A related finding in this respect is the importance of a maternal serum D3 concentration sufficient to support production of human milk capable of meeting infant needs for vitamin D.

Several of these insights have implications for the human requirement. For example, the vitamin D input needed to support an adequate amount of vitamin D in human milk has implications not just for lactation but also for human success as a species under presupplementation conditions. Inadequate vitamin D input in newborns would be expected to lead to skeletal abnormalities (for which the paleo-fossil record provides no evidence), in addition to possible consequences for immune system development.89 A total input of approximately 6,000 IU in modern humans equips them to feed their infants with a nearly full range of the nutrients needed for healthy growth.

CONCLUSION Precise quantification of vitamin D inputs, transfers, conversions, and compartment sizes are essential for a full understanding of how the human body utilizes this essential micronutrient, why it is important, and what the consequences are of an inadequate vitamin D input.

Since its founding, the U.S. Preventive Services Task Force (USPSTF) has provided firm evidential base for early detection strategies, evaluating such screening methods as mammography and prostate-specific antigen testing. Although it has also evaluated a few interventions, its predominant focus has been testing for markers that identify persons at risk who are likely to benefit from preventive action. Only recently has USPSTF entered the (mine)field of nutrition, a territory distant from screening tests and risk assessment, with different and unfamiliar landmarks.

The USPSTF now reports it is unable to find evidence for or against vitamin D deficiency testing (1), the likely reasons being the absence of a scientific consensus on both the level of vitamin D status that should be judged “deficient” and what the measurable manifestations of deficiency might be. These are also issues for many other nutrients, such as folate, ascorbate, calcium, and protein. Vitamin D may have seemed to offer a way out of this confusion because serum 25-hydroxyvitamin D [25-(OH)D] concentration is generally recognized as one of the best indices of status for any of a broad array of nutrients. Also, it is now readily measurable and widely utilized.

One of the reasons its promise has not been realized is that most studies of vitamin D efficacy have used a disease-avoidance model, which is the standard approach used by the Institute of Medicine (IOM) for most nutrients (2). Furthermore, disease prevention is the explicit focus of the USPSTF. Nevertheless, the IOM and USPSTF approaches effectively equate health with the absence of disease, an equivalence that nutritionists have long rejected. Instead, nutritionists focus on full nutrient repletion when possible. The inevitable gap between disease prevention and nutrient repletion is still largely unexplored territory. For many nutrients, it can be surprisingly wide, as suggested in this case by studies of the intake required to provide vitamin D in human breast milk in quantities sufficient to meet the needs of infants (3). The IOM’s adult requirement for vitamin D is 600 IU/d (4), which is judged to be sufficient to protect against osteoporotic fracture. In contrast, quantitative and empirical evidence indicates that vitamin D intake from breastfeeding needs to be approximately 6000 IU/d (3, 5). Although high compared with the adult recommendation, such an intake almost exactly reproduces the measured vitamin D status of contemporary Africans leading ancestral lifestyles (6). Such populations provide perhaps our best window on vitamin D levels prevailing during the millennia over which human physiology was adapted to its environment by natural selection.

Whatever the actual requirement or 25-(OH)D cutoff may be, there is another likely reason that the evidence is unclear. The USPSTF drew from systematic reviews and meta-analyses of studies of vitamin D effects, such as the one accompanying the current report (7). In general, the criteria for including studies in such reviews are methodological rather than biological. Of the 6 published biological criteria (8) for including published reports in meta-analyses, the review published in this issue met only 2 (comparable basal status and same chemical form), and several of its component studies met none. Including studies that could never have been informative in the first place (especially when they are large) inevitably biases any review toward the null.

What seems not to have been widely appreciated is that vitamin D exhibits flat response regions at both low and high values of vitamin D status, with a sharp rise in the approximate center of the physiologic range of 25-(OH)D values (8). Studies like the WHI (Women’s Health Initiative), which enrolled women with low vitamin D status values and used a vitamin D dose insufficient to move them into the response range, provide little useful information about vitamin D efficacy. Yet, precisely such studies were included in the review by LeBlanc and colleagues (7). This is not to criticize the WHI, which was designed more than 20 years ago (before vitamin D pharmacology was well-understood), but it is to criticize contemporary reviews and meta-analyses that fail to take advantage of newer information or to use critical biological criteria (8) for selection of studies for analysis of biological effects.

In addition, a disease-avoidance approach becomes problematic for micronutrients in general (and vitamin D in particular) when one understands that micronutrients do not actually cause any of the effects simplistically attributed to them. Although necessary for cell response, such micronutrients by themselves do not initiate or cause the response concerned. For example, vitamin D is a component of the biochemical apparatus that opens the genome to allow access to DNA information needed for a particular cell or tissue response. In terms of cell function, this dependence means that when supplies of the micronutrient are inadequate, cellular response is blunted. This is dysfunction, but not clinically manifest disease. Such dysfunction may indeed lead ultimately to various diseases, but disease prevention remains a dull tool for discerning the defect, and a disease-prevention approach clearly does not measure whether the organism has enough of the nutrient to enable appropriate physiologic responses, such as lactation.

Finally, and aside from the USPSTF’s findings, one must ask whether treating without first testing is sound practice. Certainly, it would be rational to do so if the condition being treated is prevalent and the treatment is safe and inexpensive. That is the case with another micronutrient, iodine, and the iodination of salt. However, the current situation is different because getting sufficient iodine generally does not require conscious adherence to a particular regimen, whereas taking vitamin D does. Usually, testing improves patient adherence because it provides patient-specific, personally applicable information. General assurances that one probably needs extra vitamin D are not as compelling a motivator as knowing one’s number. Thus, whether the practitioner adheres to the widely divergent guidelines of the IOM (4), the Endocrine Society (9), or the American Geriatrics Society (10), measuring vitamin D status seems to be warranted, not so much to diagnose deficiency but to determine patient status relative to the selected guideline.

THE NEAR-IMPOSSIBILITY OF OVERDOSING WITH VITAMIN D3 – except by persistent repeated injection: A Report in Feb 2014 from Bansai & Arora ea New Delhi show how extreme the overdose of vitamin D3 must be to cause hypercalcemic toxicity: an Asian woman given 6million iu imi over 10 days after knee surgery presented 2 months later with 6 wks of persistent vomiting, fatigue, with moderate hypercalcemic renal failure and 25OHvit D level of 150ng/ml; that normalized in 2 weeks.. So her peak level after the initial 2 weeks on an average ~50 000iu/day may have been around 500-600ng/ml.. Bansai and Aroraquote two series from endemically vit D deficient Kashmir (Pandita ea 2012 in Jammu and 2011Koul ea Srinagar) of a total 25 elderly given chronic overdoses D3 600 000iu monthly , who were found to have similar moderate hypercalcemia and renal failure with peak 25OHvit D of 100 – 300ng/ml: a mean vit D3 dose of between 20 000iu and >1million iu/day?, mean s. creat 2.5; mean 25OHvitD of 100 – 200ng/ml; mean calcium 13.1mg/dl. 20 000iu a day indefinitely in these frail small elderly averages at least 400iu/kg/day, at least 5 times the chronic recommended dose in the literature the past decades- and to boot, routinely given them with a highdose calcium supplement- when it is rather magnesium that should if any be boosted. . Koul ea do note that about 100 000iu vit D a day ongoing is required to cause hypercalcemia, the mean lethal dose being about 8million iu.

By contrast, previous reports below- eg from the Netherlands report of 2million iu single overdose in 90 year olds; and planned 600 000iu orally monthly dose in Pakistani men wasted with TB (Salhuddin ea below) showed no overdose signs. So a single loading dose of 1 to 2 million units is unlikely to give overload. By these precedents (eg 600 000iu p.o monthly- apparently official policy of the Pakistani Endocrine Society) one may in acute infections give up to 600 000iu as a loading dose (a million in an obese ill patient) in acute infection situations, then 50 000- 80 000iu weekly depending on weight, to maintain level around 90ng/ml.

Am J Clin Nutr March 2008 Pharmacokinetics of a single, large dose of cholecalciferol 100 000iu Ilahi, Armas, and HeaneyCreighton University Medical Center, Omaha, Design: followed for 4 mo, 30 subjects were supplemented with a single oral dose of 100 000 IU cholecalciferol. 10 subjects served as a control group to assess seasonal change of calcidiol. The subjects were healthy with limited sun exposure (<10 h/wk) and milk consumption (<0.47 L daily); excluded granulomatous conditions, liver disease, kidney disease, or diabetes or taking anticonvulsants, barbiturates, or steroids. Results: Serum calcidiol rose promptly after cholecalciferol dosing from a mean (±SD) baseline of 27.1 ± 7.7 ng/mL to a concentration maximum of 42.0 ± 9.1 ng/mL. Seven percent of the supplemented cohort failed to achieve 32.1 ng/mL at any time point. The highest achieved concentration in any subject was 64.2 ng/mL. The control group had a nonsignificant change from baseline of −0.72 ± 0.80 ng/mL during 4 mo. Conclusions: Cholecalciferol (100 000 IU) is a safe, effective, and simple way to increase calcidiol concentrations. The dosing interval should be ≤2 mo to ensure continuous serum calcidiol concentrations above baseline.

THE IMPORTANCE OF IMMUNOSYNERGY BETWEEN ADEQUATE ANABOLIC HORMONES- VIT D3, MELATONIN(Berman 1926, Carrillo-Vico2013), AND PROGESTERONE in planned and current pregnancy, and aging? Thangamani, Kim ea Purdue & Indiana Universitiesin J Immunol. 2014 Dec 29: Cutting Edge: Progesterone Directly Upregulates Vitamin D Receptor Gene Expression for Efficient Regulation of T Cells by Calcitriol. The two nuclear hormone receptor ligands progesterone and vit.D play important roles in regulating T cells.., we report that progesterone is a novel inducer of vit.D receptor (VDR) in T cells and makes T cells highly sensitive to calcitriol even when vit. D levels are suboptimal. This novel regulatory pathway allows enhanced induction of regulatory T cells but suppression of Th1 and Th17 cells by the two nuclear hormones. The results have significant ramifications in effective regulation of T cells to prevent adverse immune responses during pregnancy.

A recent review of vitamin D from Mike Holick (Boston Mass.) and a German team again reminds us of two opposing forces limiting natural sunshine vitamin D supply: on the one hand the skin shuts down active vit D production if the sunlight burns, while on the other, there is simply not enough sunlight beyond 35degrees latitude from the equator. Thus Germany and Canada-northern USA for example, at >45degrees north, get far too little sunlight for vit D needs ; eg London is at 51degrees north; Cape Town-Florida-San Diego, Sydney-Buenos Aires, Hawai and the Med. countries are at the 35degree south latitude. Even this close to the equator, many overdress- especially more observant religious women- and thus minimize benefit from summer sunshine.

Sunshine Cures: why did TB sanatoria work (before there were antibiotics)? was it indeed the boost of copious sunshine secosteroid antimicrobial soltriol in the skin destroying the M TB porphyrins? or was it belief, then-cleaner air, high altitude, rest, care and better nutrition?

A recent 2009 Mt Sinai NY report of a case of CTB cutaneous TB stresses how rare this skin complication is despite the increasing spread of TB with AIDS- perhaps partly because of the higher prevalence of HIV in poorer peoples in sunnier warmer ie relatively better sunshine-cholecalciferol-endowed climates.

We easily make our optimal vit D3 ~100iu/ kg per day living playing and working outdoors in warm lands. But since we dress more in cooler climates, with aging and dress-conservative cover-up tribal eg Arabic and Hasidic and Mormon customs; and avoid sunburn, and from early middle age lose 3/4 of our skin vitamin D production by 70years, we aging thus need the bulk of our vit D requirements as supplements ie ~7000iu/day or 50 000iu/week.

A century ago, TB, polio, measles, scarlatina, and syphilis were rampant, and infections rather than wars killed most – ending in the 1919 flu holocaust that devastated the family of Dr Sir Arthur Conan Doyle (whereas the Flu pandemic took just one of my parents’ score of siblings- and polio just left my Mom with a limp..)..

2014 is the centenary of recent recognition of the cod liver oil antirickets steroid factor – calciferol/soltriol -briefly misnamed “vitamin” D – by McCollum, Davis (USA 1913) and Mellanby(UK); so that in 30 years by 1945, rickets had been all but abolished in USA. But the recognition of the antirachitic factor was facilitated by discovery in the preceding decade of vitamins A, B and C. The antiscurvy benefit of fresh uncooked coloured crops (and thus their juice) had indeed been recognized for millennia – eg the Royal Navy limejuice- , but a specific micronutrient vitamin deficiency was first only recognized in 1907. Vitamin C ascorbic acid identification also took another 25years . For 90 years, it has been recognized that a lightly cooked exclusively fatty meat diet can provide enough vitamin C (let alone all micronutrients) for health in eg atheroma- and scurvy-free Eskimos and anyone who cares to eat thus (Stefansson ) .

Sadly, the lifegiving vitamins have been diluted, all but eliminated from retail bottled codliver oil, a ml of which now generally supplies perhaps only 125iu vit D, and vitamin A 1000iu … So even a tablespoon supplies only about 1200iu vit D.. The Weston Price Foundation discusses why modern commercial codliver oil is good with its balance of vits A and D– but the vitamin D level is still far too low for cooler darker countries. However we recommend, (apart from far cheaper vit D3 powder 50 000iu/1ml scoop) – a tsp cod liver oil at least 3 times a week because it is the cheapest natural- and with Scandinavian manufacturing controls, safe- source of vital EPA+DHA available as well as some vitamins A and E.

As real summer begins here between the southern oceans, cold winter in the northern hemisphere, we must constantly remind that vitamin D3 cholecalciferol is NOT an exogenous vitamin ie a biological nutrient essential (Funk’s ‘vitamine’, shortened by Jack Drummond because they are not amines to the more appropriate ‘vitamin’) in the human diet ( like vits A, B, C, E & K) because humans cannot make them. . But since we make vit D with light exposure of our skin, since most humans dont get enough sunlight on our skin, it is certainly a conditioned essential anabolic steroid, which like other anabolic steroids (the balance especially of androgens) is vital at optimal blood levels through life for optimal health, healthspan.

Unlike the real vitamins and essential minerals, Calciferol is (like eg CoQ10, alphalipoic acid, nitric oxide, EPA and DHA) made in limited quantities in humans with adequate organ function and sunshine; but none of them generally in anywhere near optimal quantities for healthspan against all diseases. So given humans’ capacity to live well to a century, we need such supplements from youth to ensure chronic health so as to die of old age in good health. .

How does this relate to the death this month of Dr Nerissa Pather? Multiresistant TB contracted on duty 12 years ago eventually killed her, whether or not such high-risk people are ever advised to take the best prevention- zinc, selenium, multivites but especially highdose vit C and D3.

D3 bio-insufficiency fragility and dysimmunity is further complicated since to correct it requires both plenty of skin sunshine exposure, eaten vitamin C and it’s daughter cholesterol, and optimal kidney and liver function. Even then optimal vitamin D3 bloodlevel and effect may be blocked by foolhardy cholesterol blockade eg statins, and by excess intake and thus bloodlevel of vitamin D2 ergocalciferol – which authorities eg in South Africa and USA still negligently promote/ dispense as the dangerously misnamed “strong calciferol”. It is indeed D3 cholecalciferol, not D2 that is the miracle sunshine strong calciferol steroid; egocalciferol dominance, like insulin and estrogen dominance, is harmful, and can and must be avoided. .

So it is increasingly apparent that, just as intake/manufacture of vitamin C the true sunshine vitamin (those colourful veg/ fruit orchards etc) , and thence cholesterol, should each be at least a few gms a day, the human (clothed indoor-dwelling) adult synthesis + intake of sunshine hormone vitamin D3 soltriol should be nearer to 10 000iu ie 250mg/day, or more practically 50 000iu vit D3 a week (at a trivial supplement cost of eg R6/month or $5 a year) for a bigger adult- especially in longer darker winter (starting with perhaps about 25000iu every fortnight for babies) .. of course balanced in most societies with the other supplements especially water, vitamin K2, zinc, selenium iodine and magnesium (and iron for children and reproductive mothers) .

So, how many more millions must suffer and die from lack of the cheapest, best, safest conditioned essential antimicrobial antioxidant anabolic nutrients available?

An undated (post 2003) Pharmacology Bulletin from Canterbury NZ at least gives conservative realistic vit D3 advice: a loading dose of D3 500 000iu , then 50 000iu/month. This compares with our routine loading dose of about 200 000 to 400 000iu to start, then 50 000iu every week or two (proportionate to body mass and illness). But Lennons here negligently still continues to advertise their Strong Calciferol datasheet (updated 2004) as calciferol- last year they in fact confirmed it is D2 ergocalciferol, not cholecalciferol. Only their websitehttp://www.ndrugs.com/?s=lennon-strong%20calciferol confirms that their strong Calciferol is D2; whereas they also make low strength D3 tabs.

From today’s press “The South African Medical Association (SAMA) extends heartfelt condolences on the passing of 38yr old Dr Nerissa Pather on 18th December 2014 . Whilst on community service at a Kwazulu Natal clinic, Dr Pather contracted well-publicised multi-drug resistant spinal TB in 2002 , that rendered her paralyzed and in constant pain. The loss to a communicable disease acquired in the course of duty is an incalculable tragedy. SAMA reiterates its call to all health departments and facilities to ensure that basic TB prevention methods are available to all healthcare workers in our facilities. Sadly, this is not the case in many of our hospitals and clinics and continues to place health professionals at enormous risk. The potential consequences of infection and even acquiring drug resistant TB are tragically evident in the death of Dr Pather. SAMA bows its head to a colleague who has paid the ultimate price in caring for her fellow human beings.”

The tragedy is that with general authoritarian nihilism about universal vitamin supplements- some calling their promotion quackery- unrecognized deficiency eg vit D3, rickets, and vit C scurvy are on the increase even in the more affluent eg USA and in sunnier climates- especially with increasing geriatrics and the frail surviving with eg HIV, TB, cancer, chronic bowel disease, gross overuse of warfarin (vit K deficiency) and statin (CoQ10 deficiency) etc. .

Vitamin D Deficiency in Critically Ill Patientsis rarely considered or treated .. N Engl J Med 2009 Lee, Eisman & Center studied vitamin D status in ICU patients referred to St. Vincent’s Hospital, Sydney in 2007. Among approximately 1100 ICU patients per year, the mean 25-hydroxyvitamin D in 42 referred patients was ~17ng per milliliter, with a high prevalence of hypovitaminosis D . Moreover, three patients died (from metastatic thymic carcinoma, glioma, and lymphoma), and had undetectable levels of 25-hydroxyvitamin D. The current study of ICU patients reveals high prevalence of hypovitaminosis D that was associated with adverse outcomes, independently of hypocalcemia and hypoalbuminemia. Supplementation with vitamin D (at a mean dose of 820 IU per day) before admission was not protective. Vitamin D deficiency is associated with increased mortality.However, vitamin D has pleiotropic effects in immunity, endothelial and mucosal functions, and glucose and calcium metabolism. The association between hypovitaminosis D and common conditions (e.g., the systemic inflammatory response syndrome, septicemia, and cardiac and metabolic dysfunctions) in critically ill patients may be important. Vitamin D–deficient and vitamin D–insufficient states may worsen existing immune and metabolic dysfunctions in critically ill patients, leading to worse outcomes. A total of 17% of ICU patients in our study had undetectable levels of vitamin D. hypocalcemia was identified as a reason for referral in only 5% of the patients. These findings highlight the need for consideration of vitamin D status and supplementation in patients in the ICU.

Arch Intern Med. 2008;168:1629-37 25-hydroxyvitamin D levels and risk of mortality in the general population. Melamed , Astor ea. Albert Einstein College of Medicine, NY tested the association of low 25(OH)D levels with all-cause, cancer, and cardiovascular disease (CVD) mortality in 13 331 nationally representative adults 20 years or older from the NHANES III linked mortality files.In patients on dialysis, therapy with vitamin D agents is associated with reduced mortality. Observational data suggests that low (25[OH]D) are associated with diabetes mellitus, hypertension, and cancers. However, whether low serum 25(OH)D levels are associated with mortality in the general population is unknown. Participant vitamin D levels were collected from 1988 through 1994, and individuals were passively followed for mortality through 2000. RESULTS: In cross-sectional multivariate analyses, increasing age, female sex, nonwhite race/ethnicity, diabetes, current smoking, and higher body mass index were all independently associated with higher odds of 25(OH)D deficiency (lowest quartile of 25(OH)D level, <17.8 ng/mL , while greater physical activity, vitamin D supplementation, and nonwinter season were inversely associated. During a median 8.7 years of follow-up, there were 1806 deaths, including 777 from CVD. In multivariate models , compared with the highest quartile, being in the lowest quartile (25[OH]D levels <17.8 ng/mL) was associated with a 26% increased rate of all-cause mortality (mortality rate ratio, 1.26; 95% CI, 1.08-1.46) and a population attributable risk of 3.1%. The lowest quartile of 25(OH)D level (<17.8 ng/mL) is independently associated with all-cause mortality in the general population.

Subst Abuse Rehabil. 2014 Dec 10;5:121-7. Effects of different doses of testosterone on gonadotropins, 25-hydroxyvitamin D3, and blood lipids in healthy men.Gårevik, Ekström ea. At the Karolinska Inst Sweden, Twenty-five healthy male volunteers aged 27-43 years were given 500 mg, 250 mg, and 125 mg of testosterone enanthate as single intramuscular doses. All doses investigated suppressed the LH and FSH concentrations in serum. LH remained suppressed 6 weeks after the 500 mg dose. These results indicate that testosterone has a more profound endocrine effect on the hypothalamic-pituitary-gonadal axis than was previously thought. There was no alteration in 25-hydroxyvitamin D3 levels after testosterone administration compared to baseline levels. The 250 and 500 mg doses induced decreased concentrations of ApoA1 and HDL, whereas the lowest dose (125 mg) did not have any effect on the lipid profile.

BoneKey Rep 2014:3:479:p1-8History of the discovery of vitamin D and its active metabolites Prof Hector deLuca graphically tells the story of the discovery of the lifesaving sun steroid cholecalciferol D3 between 1913 and its chemical formula in 1937, and then its’ functional chemistry through the 1970s. Until the preWW1 era, nutrition was blocked by false German dogma (von Liebig ea) that an adequate diet consisted of just 12% protein, 5% mineral, 10–30% fat and the remainder as carbohydrate. Such a diet – eg with polished rice, sugar and milled wheat- was shown to rapidly kill humans and animals ie without the essential micronutrient vitamins. .

Belief that this defined an adequate diet was to resurface in postWW2 Western capitalism in USA and UK through the twentieth century.

Then British, Continental and USA nutritional scientists started tearing that myth apart- and today we have the revelation that we need the ancient diet: just an adequate amount of first-class protein (but not soya); the bulk of needed nutritional calorie energy as natural fat (balanced omega 3: omega 6 and saturated medium chain triglycerides, but not transfats which are synthetic), with the balance of energy carbs and protein supplied by coloured veggies; supplying enough of the essential minerals, vitamins and marine oils.

But since most humans are no longer able to live off unpolluted unfarmed marine life or natural rotation-crop and grazed meat farming, but work indoors during daylight hours or, worse, disruptive night shifts, and city deathrates have risen steadily on the mythical low(but synthetic) fat, high carbs diet invented as dogma by Ancell Keys and his food factory cronies, the natural fat and -coloured-veggs -dominant diet rapidly re-establishes itself, with vigorous vit D3 and multivits to supplement the depleted and polluted fastfood chain.

update 22 Dec 2014: as the solstice rolls by, infections especially viral flourish north and south, from flu to gastro , HIV to ebola; HPV to HZV to childhood exanthems;

so more reason to aim for optimal growth, mental and physical health with the peak anabolic antidepressant energizing anticancer antiinfective steroid – cholecalciferol D3 – intake and levels. About 65 000iu a week (with my multivit-multimineral combo) puts my measured trough 25OHvit D bloodlevel at 92ng/ml with normal blood calcium. Women can live long without much androgen apart from frail bones, but not well without vigorous cholecalciferol D3 intake. Humans who live mostly bare mostly outdoors- us naked apes- most of the year closer to the equator make plenty of D3 from sunshine; but the darker our skins, the sooner vit D production shuts down; so most of us need vigorous D3 supplement costing perhaps US$6 a year retail. .

update 19 Nov 2014 when this column on vit D started 5 years ago, there were 46000 vit D entries on Pubmed- this has mushroomed 40% to 61000 (compared now to 46000 on vit A; to 53000 on vitamin C; 37000 on vitamin E; 17000 on vit K; and 133000 on all the 8 B vitamins ); whereas in 2009 there were 272500 entries on all vitamins– now up only 22% to 335 000. ie the papers on the secosteroid vitamin D have risen at double the rate of the vitamins.. (D3 C27H44O and D2 C28H44O, vs testosterone C19H28O2).

As the end-of-year solstice approaches, its time to review the crucial role of giving vigorous doses of vitamin D3, whether via non-burn sunshine, or via the correct lowpressure tanning bed, or directly as vitamin D3 (not vit D2) supplement as appropriate TOGETHER WITH A MULTINUTRIENT PLUS EXTRA MAGNESIUM AND VIT K2. . Ironically, dermatologists would recommend vit D supplement not suntan for what many consider the wrong reason- that suntanning does more harm than good, which it doesnt. :

3. Swanson, Barrett-Connor, ea USA & Belgium May 2014: In a cohort of older men, Higher 25(OH)D2 is associated with lower 25(OH)D3 and 1,25(OH)2D3, suggesting that vitamin D2 may decrease the availability of D3 and may not increase calcitriol.

5. Biancuzzo, Holick ea Boston Mass. 2013 Serum concentrations of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in response to vitamin D2 and vitamin D3 supplementationin healthy adults 18 to 79 years consuming 1000 IU vitamin D2 or vitamin D3 per day for 11 weeksat end of winter was analyzed. Of the adults, 82% were vitamin D insufficient (serum 25-hydroxyvitamin D [25(OH)D <30 ng/mL]) at the start of the study. Administration of vitamin D2 and vitamin D3 induced similar increases (from baseline ~20ng/ml 25OH vit D) in total 25(OH)D as well as in 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, respectively. Compared with placebo and adjusting for baseline levels, 1000 IU daily of vitamin D2 was associated with a mean increase of 7.4 pg/mL (95% confidence interval, 4.4-10.3) in 1,25(OH)2D2, and decrease of 9.9 pg/mL (-15.8 to -4.0) in 1,25(OH)2D3. No such differences accompanied administration of 1000 IU daily of vitamin D3.

7. Sempos CT1, Picciano MF ea . USA J Clin Endocrinol Metab. 2013 Jul;98(7):3001-9..Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES.A reverse J-shaped association between serum 25-hydroxyvitamin D (25[OH]D) concentration and all-cause mortality was suggested in a 9-year follow-up (1991-2000) analysis of the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994). We repeated the analyses with 6 years additional follow-up in 15 099 participants aged ≥ 20 years with 3784 deaths, to evaluate whether the association persists through 15 years of follow-up. The reverse J-shaped association became stronger with longer follow-up and was not affected by excluding deaths within the first 3 years of follow-up. Similar results were found from both statistical approaches for levels <20 through 119 nmol/L. Adjusted RR (95% confidence interval [CI]) estimates for all levels <60 nmol/L were significantly >1 compared with the reference group. The nadir of risk was 81 nmol/L 32pg/mL (95% CI, 73-90 nmol/L 29-36pg/ml). The association appeared in men, women, adults ages 20 to 64 years, and non-Hispanic whites but was weaker in older adults. A reverse J-shaped association between serum 25(OH)D and all-cause mortality appears to be real. It is uncertain whether the association is causal.

11 Armas , Heaney ea.Creighton Univ Nebraska. J Clin Endocrinol Metab. 2004 ;89:5387-91. VitaminD2 is much less effective than vitaminD3 in humans.Vitamins D(2) and D(3) are generally considered equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitaminD(2)) available in the U.S. market. Relative potencies of vitamins D(2) and D(3) were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the serumvitaminD over 28 d.. The two calciferols produced similar rises in serum concentration, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60 ng.d/ml for vitaminD(2) and 204 for vitaminD(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1. VitaminD(2) potency is less than one third that of vitaminD(3). Physicians resorting to use of vitaminD(2) should beware of its markedly lower potency and shorter duration of action relative to vitaminD(3)

12 Trang, Vieth ea University of Toronto, Am J Clin Nutr.1998 . Evidence that vitaminD3 increases serum25-hydroxyvitaminD more efficiently than does vitaminD2. In all species tested, except humans, biological differences between vitamins D2 and D3 are accepted as fact. Subjects took 260 nmol (approximately 4000 IU)vitaminD2 (n=17) or vitaminD3 (n=55) daily for 14 d. With vitaminD3, mean (+/-SD) serum 25(OH)Dincreased from 41+/-18 nmol/L before to 65+/-17 nmol/L after treatment. With vitaminD2, the 25(OH)D concentration went from 434+/-18 nmol/L before to 57+/-13 nmol/L after. The increase in 25(OH)D with vitaminD3 was 23+/-16 nmol/L, or 1.7 times the increase obtained with vitaminD2 (14+/-11 nmol/L; P=0.03). There was an inverse relation between the increase in 25(OH)D and the initial 25(OH)D concentration. In the highest tertile [25(OH)D >49 nmol/L] the mean increase in 25(OH)D was 13.3 nmol/L (P < 0.03 for comparison with each lower tertile). Although the 1.7-times greater efficacy for vitaminD3 shown here may seem small, it is more than what others have shown for 25(OH)D increases when comparing 2-fold differences in vitaminD3 dose. The assumption that vitamins D2 and D3 have equal nutritional value is probably wrong and should be reconsidered.

13. Hymøller L1, Jensen SK.Denmark J Dairy Sci. 2011;94:3462-6. Vitamin D₂ impairs utilization of vitamin D₃ in high-yielding dairy cows in a cross-over supplementation regimen. D(3) given after D(2) is less efficient at increasing the plasma status of 25(OH)D(3) than D(3) given without previous D(2) administration.

A Vitamin D Expert’s Take on the Latest Warning to Stay Out of the Sun to Avoid Skin Cancer

By Dr. Mercola 16/11/2014The US Surgeon General recently came out with a warning on skin cancer,1 claiming that the sun is dangerous and that you need to stay away out of it.

pioneer Dr. John Cannell, founder of the Vitamin D Council, has dedicated a large part of his professional career to the study of vitamin D and its health benefits, and he has a warning of his own to those who take this narrow-minded advice to heart.

It’s worth noting that the acting Surgeon General, Boris Lushniak, is a dermatologist. And of all the medical specialties out there, dermatologists are clearly the most biased against sun exposure, & as a result, against vitamin D.

This isn’t surprising, since they primarily see the ill effects of sun overexposure. But in taking an overly narrow view, the advice to avoid sun exposure as much as possible can have equally if not greater adverse health effects. The Connection Between Sun Exposure and Skin Cancer Unquestionably, UV radiation can be dangerous; it can increase your risk for certain skin cancers such as squamous cell, basal cell, and melanoma. But there are significant differences even between these cancers, and appropriate sun exposure may actually be more beneficial than detrimental in some cases. Dr. Cannell explains:

“Squamous cell carcinoma is clearly associated with chronic sun exposure. It is more common on the face, the hands, and the scalp.

It is related to radiation burden over your lifetime, and together with basal cell carcinoma, which is sort of intermediate, it accounts for approximately 1,500 deaths a year in the United States…

Basal cell is sort of intermediate. There are studies showing that it is associated with chronic sun exposure, and there are studies showing that it’s not associated with chronic sun exposure.

And then there’s melanoma, which is responsible for almost 9,000 deaths a year and is the deadly skin cancer that is feared. The relationship that melanoma has with the sun is quite complicated.

It is clearly associated with sunburn, especially sunburns when you’re young (that’s incontrovertible) or sunburns in a sun tanning bed.”

However, there are at least two studies showing that melanoma is more common in indoor workers than outdoor workers. And the most likely places for melanoma to appear are actually NOT the face and the hands like squamous cell carcinoma, but rather the lower back and the upper leg—areas that are usually not chronically sun-exposed.

According to Dr. Cannell, there’s a vocal minority in the dermatological community that thinks the emphasis dermatologists have on avoiding sun exposure is wrong, because while sunburn is a risk factor, chronic sun exposure is not.

“A number of studies show that chronic sun exposure is related to melanoma, but they don’t separate out the sunburns, which is very hard to do because you have to do that by memory,” Dr. Cannell says. Two Decades-Long Study Finds Sun Avoidance Doubles Risk of Death Dr. Cannell notes a recent study2 done in Sweden, which followed nearly 30,000 middle-aged to older women for up to 20 years. The average follow-up was 15 years.

At the outset, they asked a number of questions about sun exposure, such as: Do you sunbathe? Do you take vacations in sunny areas in the winter? Do you garden with short sleeves and shorts? And, do you use sunbeds?

What they found, and this appears to be the only study of this kind, is that the women who avoided the sun were twice as likely to die over the course of the study. The researchers attributed this finding to a vitamin D mechanism.

What this study actually shows is that chronic sun exposure appears to be associated with less mortality. It’s also the first study to show that women who use tanning beds live longer than those who don’t.

This is in direct conflict to what almost every dermatologist will say, including the Surgeon General. It’s unfortunate, but the danger of almost any specialist is that they don’t take the broader perspective.

What the Surgeon General and almost every other dermatologist fail to take into account is the overall mortality, which is referenced in this recent study. Risk-Benefit Analysis In addition to this study, dozens of others document the benefits of appropriate sun exposure. This includes a reduced risk of about 16 different cancers of Dr. Garland’s studies suggest this reduction is close to 50 percent.

So many hundreds of thousands of people are put at risk from other cancers as opposed to 10,000 people who are dying from skin cancer caused by sunburn. It’s really a matter of making an educated risk-benefit analysis.

“When you do a risk-benefit analysis and you look at all the data we have, the risk in my opinion appears to be in those who avoid the sun,” Dr. Cannell says.

“Now, if you avoid the sun, your risk for non-melanoma skin cancer goes down. That’s clear. But if you look at studies of either latitude or of 25-hydroxyvitamin D levels in relation to cancer, you find this inverse relationship: the higher the vitamin D level, the lower the internal cancer rate.”

Dr. William Grant of Sunlight, Nutrition, and Health Research Center (SUNARC) estimates that if everyone in the United States had a vitamin D level of 40 nanograms per milliliter (ng/ml), it would save approximately 150,000 lives a year.3

That’s 100 times the rate of squamous cell cancers, which are the only ones that are definitively linked to UV exposure. In Canada alone, it is estimated that 37,000 lives a year are lost due to vitamin D deficiency.4Also, use of sunscreen has risen in the last 30 years, so if dermatologists were correct, there should be a decrease in stage 1 melanoma. But there’s not. As sunscreen use increased, stage 1 melanoma diagnosis increased…

“It’s thought that by blocking out UVB, patients are able to stay out in the sun longer than they would have otherwise and expose themselves to the more dangerous, or at least potentially dangerous, UVA radiation that’s in the sunshine,” Dr. Cannell says. “What we recommend is what’s called safe, sensible sun exposures. The Australian Cancer Council now recommends the same thing. I think in England there’s now a change in their recommendation from strict sun avoidance to some safe, sensible sun exposure. There are some movements in large organizations to realize that safe, sensible sun exposure is a healthy thing.”

How Much Sun Exposure Is Sensible? On its website, Cancer Research UK reports that “by enjoying the sun safely and avoiding sunburn, people can reduce their risk of skin cancer and enjoy the beneficial effects of the sun.” Cancer Research UK’s sun advice is endorsed by the British Association of Dermatologists, Cancer Research UK, Diabetes UK, the Multiple Sclerosis Society, the National Heart Forum, the National Osteoporosis Society, and the Primary Care Dermatology Society. The UK National Health Service5 also recommends sensible, individualized sun exposure to help optimize vitamin D.

It’s important to recognize is how quickly sunlight can make vitamin D in the skin. You don’t need to be outside for hours on end. But you do need more than just a few minutes of sun on your face and arms. According to Dr. Cannell, sunbathing at solar noon in the summer, at most latitudes in the United States you will make between 5,000-10,000 international units (IUs) of vitamin D within 30 minutes.

“You can ask yourself why nature would evolve a mechanism that made so much vitamin D so quickly,” Dr. Cannell says. “When I thought about that question, the only answer I could come up with is nature did it for a good reason. The organism needs vitamin D, so the system in the skin evolved to make it very quickly upon exposure to sunlight.

We recommend full-body sun exposure for up to anywhere from a few minutes to 30 minutes every day. On those days when you cannot get a full-body sun exposure, we recommend a vitamin D supplement or sensible exposure in a low-pressure UVB bed.”

If you’re getting regular sun exposure, I think the need for an oral supplement is really minimal to non-existent. When you swallow a pill, there’s no self-regulating ability. Your body doesn’t have an ability to selectively limit its absorption. But your skin has the ability to control how much vitamin D is being produced based on how much is in your blood.

I personally have not taken oral vitamin D for five years and my level runs from 50-70 g/ml. Lifeguards, roofers, and gardeners who work with their shirt off, all tend to have levels between 40 and 80 ng/ml in the summer. This also brings up an interesting question about the difference between normal and natural. Normal vitamin D levels are an average of what indoor workers have in both winter and summer. Natural are levels of a population with widespread sun exposure. The latter is going to be closer to ideal, or optimal.

References for establishment of optimal levelsThere are also other reasons to strive for sun exposure rather than swallowing a pill. As noted by Dr. Cannell, aside from producing vitamin D, sunlight also affects nitric acid levels and endorphins in the skin. Researchers at the University of Wisconsin recently discovered that there may be a system at 311 nanometers that is separate from the vitamin D system (which is at 298 nanometers), and that there may be an entirely new undiscovered biochemical system in the skin that makes yet another substance, besides vitamin D. Time will tell what comes out of that research, but there are indications that sunlight may be responsible for other biological processes that are unrelated to vitamin D production.

Dr. Cannell’s Recommendation on Tanning Beds There are basically two
types of tanning beds:

1. High-pressure UVA beds. They tan you the quickest because it’s UVA that tans the skin. They contain only a limited UVB spectrum, and will therefore give you color but not much vitamin D

Low-pressure beds, which contain less UVB than sunlight at most latitudes, but still contain a significant amount of UVB. These are the beds Dr. Cannell recommends, provided you’re using a sensible approach that avoids sunburns. It’s important to realize that you can easily get burned after only a couple or a few minutes when using a tanning bed

Another important factor when selecting a tanning bed is the type of ballast it employs, to avoid excessive electromagnetic field (EMF) exposure. Most tanning units use magnetic ballasts to generate light. These magnetic ballasts are well known sources of EMF fields that can contribute to cancer. If you hear a loud buzzing noise while in a tanning bed, it has a magnetic ballast system. I strongly recommend you avoid magnetic ballast beds, and restrict your use of tanning beds to those that use electronic ballasts.

On days you cannot get either regular sun exposure or use of a tanning bed, Dr. Cannell suggests taking 5,000 IUs of vitamin D3. Other vitamin D experts recommend similar amounts. It’s worth noting that, according to the federal government’s Food and Nutrition Board (FNB), the no observed adverse effects level (NOAEL) of vitamin D is 10,000 IUs a day. This means there has never been a replicated reliable study showing that 10,000 units a day is in any way detrimental.

Many individuals who have reported side effects from taking high doses of oral vitamin D have noticed that when they supplemented with magnesium, they were able to tolerate the high oral doses of vitamin D. Dr. Carolyn Dean has written in her book, The Magnesium Miracle, that she has seen this so many times that she doesn’t advise taking more than 2,000 units of vitamin D without magnesium supplementation. Be sure to also have an adequate amount of vitamin K2 along with D to slow the progression of arterial calcification. Remember though that the best form of vitamin D is the one your body produces when it is exposed to sunlight that has sufficient amounts of UVB.

Five Tips to Get an Appropriate, Sensible Amount of Sun Again, sunshine offers substantial health benefits, including vitamin D production, but you do need to exercise a few simple precautions to protect yourself from overexposure. Virtually all of the harm from sun exposure is related to sunburn. Here are my top five tanning tips: * Expose large amounts of your skin (at least 40 percent of your body) to sunlight for short periods daily. Optimizing your vitamin D levels may reduce your risk of as many as 16 different types of cancer, including pancreatic, lung, ovarian, breast, prostate, and skin cancers. If using a sunscreen, give your body a chance to produce vitamin D before you apply it. *When you’ll be in the sun for longer periods, cover up with clothing, a hat, or shade (either natural or shade you create using an umbrella). *Consider the use of an “internal sunscreen” like astaxanthin to gain additional sun protection. Astaxanthin is a potent antioxidant (and pigment) produced by marine algae in response to their exposure to UV light. Typically, it takes several weeks of daily supplementation to saturate your body’s tissues enough to provide protection. *Consuming a healthy diet full of natural antioxidants is another useful strategy to help avoid sun damage. Fresh, raw, unprocessed vegetables and fruits deliver the nutrients that your body needs to maintain a healthy balance of omega-6 and omega-3 oils in your skin, which is your first line of defense against sunburn. Vegetables also provide your body with an abundance of powerful antioxidants that will help you fight the free radicals caused by sun damage that can lead to burns and cancer.

How Vitamin D Performance Testing Can Help Optimize Your Health A robust and growing body of research clearly shows that vitamin D is absolutely critical for good health and disease prevention. Vitamin D affects your DNA through vitamin D receptors (VDRs), which bind to specific locations of the human genome. Scientists have identified nearly 3,000 genes that are influenced by vitamin D levels, and vitamin D receptors have been found throughout the human body.

14 Oct 2014 update: MORE ON OPTIMAL VITAMIN D3 DOSE, AND THE DIFFICULTY OF ACHIEVING CLINICAL OVERDOSE: Four new reports highlight how difficult, and important it is to achieve adequate optimal bloodlevels of vitamin D with vigorous vitamin D3 supplements, let alone overdose with any significant adversity: note three used the recommended vitamin D3, not the long-condemned mislabeled Lennons/Aspen vitamin D2 (which is misleadingly labelled “caciferol” without disclosing that it is D2 not D3). Even a single 2 million iu overdose of vit D3 in nonagenarians had no adverse effect-since the bloodlevel was back to zero by 3 weeks, thats above 100 000iu/day on average….

van den Ouweland , Vollaard ea Nijmegen, The Netherlands in BMC Pharmacol Toxicol. 2014 Sep 30 describe Pharmacokinetics and safety issues of an accidental oral overdose of 2,000,000 IU of vitamin D3 in two nonagenarian nursing home patients: a case report. Oral overdose of 2,000,000 IU of vitamin D3 in two nonnagenarian nursing home patients was monitored from 1 hr up to 3 months . Peak blood 25(OH)D3 concentrations were observed 8 days after intake (210 and 162ng/mL, respectively (ref: 20-80 ng/mL), followed by a rapid decrease to undetectable levels after day 14. Remarkably, plasma calcium levels increased only slightly up to 2.68 and 2.73 mmol/L, respectively (ref: 2.20-2.65 mmol/L) between 1 and 14 days after intake,; phosphate and creatinine levels remained within reference range. No adverse clinical symptoms were noted. CONCLUSION:A single massive oral dose of 2,000,000 IU of vitamin D3 does not cause clinical toxicity requiring hospitalization. Toxicity in the long term cannot be excluded as annual doses of 500,000 IU of vitamin D3 for several years have shown an increase in the risk of fractures. This means that plasma calcium levels may not be a sensitive measure of vitamin D toxicity in the long term in the case of a single high overdose.

As previously reported, to avoid dehydration stones and vascular calcification – especially in hot dry climates – , the precautions with vigorous vit D3 are to add some vit K2 and magnesium to the supplement, and maintain good water intake .

The fourth current paper, from Morocco, reports inexplicable use of dangerous massive dose of vit D2 in neonates- amounting to about 120 000iu/kg ie about 12 times the maximum adult dose reported : Hmami , Bouharrou ea Morocco University, Arch Pediatr. 2014 Oct;21:1115-9. [Overdose or hypersensitivity to vitamin DVitamin D intoxication with severe hypercalcemia is rare in the neonatal and infancy period. 9 babies between ages of 25 and 105 days were admitted for treatment of severe dehydration 8 to 15% with hypercalcemia, with preserved diuresis and loss weight between 100 and 1100 gm secondary to taking 600,000 units of vitamin D (Sterogyl(®). The pregnancies & deliveries were normal. Clinical signs were dominated by weight loss, vomiting, and fever. The vitamin D values in nine patients were toxic (mean 220: 139 – 300 ng/mL, ; normal >20ng/mL; toxicity if >100ng/mL). Nephrocalcinosis was shown in seven patients. DNA study in eight patients, did not reveal a mutation of the vitamin D 24-hydroxylase gene (CYP24A1). Treatment consisted of intravenous rehydration with diuretics and corticosteroids. Serum calcium returned to normal range within 4-50 days, with weight gain progressively over the following weeks. The follow-up (2 years for the oldest case) showed persistence of nephrocalcinosis. Genetic susceptibility and metabolic differences appear to modulate the threshold of vitamin D toxicity. However, respect for recommended doses, recognized as safe in a large study population, reduces the risk of toxicity.

VITAMIN D3 DOSE:We get excellent results in outpatient adults with loading oral dose of vit D3 of about 200 000 to 400 000iu depending on illness severity and body mass; then pro rata about 50 000iu per week till better, tapering to fortnightly when well; pro rata in kids. We monitor calcium and 25OH vitamin D3 levels occasionally if affordable – but with the tapering regime, and published data, do not see or expect hypercalcemic problems from a mean conservative weekly maintenance dose of about 3500iu/d longterm, with predicted bloodlevel of 25OHvitD of about 35-40ng/ml. As a senior with average chronic dis-ease load, I take ~63 000iu vit D3 weekly, but double it occasionally if I do get a bad cold; so I never miss a day’s work; recent stress-related shingles (2nd attack in 30 years) was just a nuisance, settled in 3 weeks with this regime plus multigrams of buffered vit C a day; oral lysine and alphalipoic acid each about 1/2 gm/day; and for a few days some weak steroid and humic acid cream topically for the neuritis and blistering, which has already healed to almost invisible. This week at a family practice clinic I saw two successive women with shingles – now a frequent occurrence, even without HIV…

Khan in Toronto in OHDM this September describes a ~60yr old man with tongue cancer who was treated inter alia with Vit D3 10 000iu a day; after a year his 25oH vitD level was ~106ng/ml, when his dose was halved; his dose response bore out the general experience that at average adult mass, vit D level rises by about 10ng/ml for every 1000iu vit D3 per day or pro rata dose weekly etc eg 50 000iu/wk or 100 000iu fortnightly may give average vit D level of ~70ng/ml. .

Singh & Bonham 2014 at Kansas University describe A Predictive Equation to Guide Vitamin D Replacement Dose in Patients. “The recommended daily allowance for vitamin D is grossly inadequate for correcting low serum concentrations of 25-hydroxyvitamin D in many adult patients. In their population (average BMI 31.5) ,about 5000 IU vitamin D3/day is usually needed to correct deficiency, and the maintenance dose should be ≥2000 IU/day. The required dose may be calculated from the predictive equations specific for ambulatory and nursing home patients” A BMI of 31.5kg at a mean height of about 1.7m gives a mean weight of 91kg, which at the consensus daily vit D3 dose of 80iu/kg/d totals ~7100iu/d or 50 000iu/wk- perhaps a reasonable maintenance dose for winter, half that in summer if reasonable weekly sun exposure. .

29 Sept 2014: As detailed elsewhere in this column, there is at least 70 years of strong experience worldwide that all microorganism infections are greatly diminished by natural prevention (not synthetic vaccines loaded with toxic heavy metals and allergenics eg egg) , and easily treated ie thrown off, with vigorous immune-boosting supplements: (mega)grams a day of vitamin C or as kgs/day of fresh produce; vitamin D3 80+ iu/kg/d to >10 000iu/d ie 300 000 to 600 000iu loading dose; then +-50 000iu/wk, plus plenty of skin exposure to sunshine; iodine; zinc; selenium; silver; the other vitamins; Ecchinacea etc. This applies both to acute and chronic infections and degenerative conditions.

To be used in highrisk cases eg MERS, AIDS, ebola etc: The landmark trial Effect of High-Dose Vitamin D3 on Hospital Length of Stay in Critically Ill Patients With Vitamin D Deficiency– The VITdAL-ICU Randomized Clinical Trial by Amrein, Dobnig ea , published today in JAMA from Austrian hospitals is most encouraging about the immense value of vigorous dose and bloodlevels of vitamin D3 against all types of severe disease. The dose used in this trial (loading dose 540 000iu =~18000iu/d 1st month, but averaging only ~8000iu/d in the first 3mo) did not achieve vigorous vit D bloodlevel, presumably because the loading dose of vit D3 in oil (540 000iu) was given by tube into the stomachs of critically ill patients; it would have better been given by transdermal injection, or else a much higher loading gastric dose given so as to speedily achieve a bloodlevel of around 70 (60 to 80) instead of half of this that was achieved in the crucial first few weeks . “from May 2010 through September 2012 at 5 ICUs the trial recruited 492 medical (60%) and surgical (40%) critically ill adult white patients , 35% women, BMI mean 27, mean age 64.6 years (SD, 14.7) with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3540 000 IU, or placebo given orally or via nasogastric tube; ; followed by monthly maintenance doses of 90 000 IU for 5 months- ie= about 18000iu/day for the first mo, then 90 000iu mthly ie only 3000iu/d. . RESULT: on placebo the 25hydroxyvit D3 level doubled from 13 at baseline to 17 at a month to 26ng/ml at 6mo.. By contrast, on vit D3 supplement it doubled to 34 at days 3 and 7 and day 28, but up to 46 at 6 months ie only 80% higher than the control group – thus 1/3 to 1/2 of the optimal target; with this, where 100% of patients were below 25OHvitD at baseline ie on admission to ICU, by 7 days, 87% were still in this bracket and none above 60ng/ml on placebo vs 25% below 20 and 13% above 60 on vit D3; and by 6mo 35% were still that low on placebo, vs 5% at that low, but 22% above 60 on vit D3.So it is not surprising thatMedian hospital stay 20 days was not significantly different between groups Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28% for vitamin D3 vs 35% for placebo; hazard ratio [HR], 0.81 P = .18; 6-month mortality: 35.0% for vitamin D3 vs 42.9% for placebo; HR 0.78 P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 19.5 days. Hospital mortality was significantly 40% lower with 28 deaths among 98 patients (28.6% ) for vitamin D3 compared with 47 deaths among 102 patients (46.1% ) for placebo (HR, 0.56 P for interaction = .04), but not 6-month mortality (34.7%] for vitamin D3 vs 50.0% for placebo- ie 31% lower; HR, 0.60, P for interaction = .12). No serious adverse events were observed. The highest 25-hydroxyvitamin D levels measured were 107 ng/mL on day 7 and 106 ng/mL at month 6- well below the theoretical minimum toxic threshold of 150 or 250ng/ml..”

As Salahuddin ea note, the good results in Pakistan in only 3 months with vigorous INITIAL dose vit D3 contrasts with Two recently published large randomised, controlled trials of conservative vitamin D3 over months that achieved far lower blood vitamin D levels found no difference in clinical outcomes or mortality after 400,000IU of 25-hydroxyvitamin D3 or placebo were given by Martineau ea in London, UK to 146 pulmonary TB patients – where mean (trough or midpoint) vit D level (after 100 000iu vitamin D(3) or placebo at baseline and 14, 28, and 42 days after starting standard tuberculosis treatment) – was surprisingly only 40ng/ml at 56days – ie after a mean of 7000iu/d by 56 days, vs 10ng/ml on placebo)- less than half of the bloodlevel achieved on vit D3 in the Pakistan trial.

So the Austrian ICU patients would undoubtedly have done much better if given more effective (ie in critically ill pts intramuscularly imi or subcutaneously) loading dose like the Salhuddin trial did.

TIME To SWOP FROM MISNAMED “STRONG CALCIFEROL” VIT D2 TO THE REAL VIT D3: as the winter solstice approaches here, with fierce weather linking to the expected influenza-like outbreak (while the MERS-CoV outbreak abates with summer in the severely vitamin D deficient Saudi Arabians), a new major study shows the supremacy of vitamin D3 for supplementation, and confirms that vitamin D2 benefit if any is so mediocre as to be unethical..

Its sad that despite the strong evidence against using vitamin D2 supplement discussed last year, it seems no one acted on it despite the confirmatory paper from Bergen of last September.

Thus vit D3 is again confirmed as four times as potent as D2. But crucially, that giving vit D2 may actually SUPPRESS the optimal serum vit D3 level.

We health professionals with our highly vulnerable populations in South Africa and worldwide (epidemic/endemic HIV, TB, cancer, drug addiction, MERS-CoV, asthma, diabetes, cardiovascular, malnutrition, alcoholism and violence) therefore surely have no choice but to swop promptly from prescribing vit D2 “Strong Calciferol” (a dangerous misnomer) to prescribing vitamin D3 at vigorous dose (with if possible occasional blood level check of 25OHvit D3)- at a trivial imported and distributed cost (100cws) to South African state clinics of perhaps<1/4 of the cost of D2 eg R1 per patient per month for a conservative 100 000iu monthly (ie after an appropriate germicidal loading dose of eg 3000 iu/kg) if not the more realistic dose double that- still at only eg US$0.2 a month.

Health Authorities everywhere have an obligation to enforce the use of vitamin D3 and not vitamin D2 globally ..

update 3 Sept 2014: while the MERS outbreak in Arabia may at last be dying down, real highly infections plagues eg ebola malaria cholera typhoid, MRSA, TB and HIV etc continue rampant, maiming and killing even more than the manmade wars raging on some continents. .

So it is ironic – or typical of the couldnt-care-less greedy politicians and potentates who run the world- that the medical authorities they employ worldwide apparently continue to ignore the dramatic benefits of at least safe antimicrobial supplements like multivite, zinc, iodine, selenium, and especially vigorous dose vitamin D3 at negligible cost, and highdose buffered vitamin C to tolerance, and colloidal silver.

We quote above trials and evidence that oral vit D2 may be actually harmful, that it is vit D3 in vigorous dose that is needed to at least treble if not quadruple the blood vit D level from the usual deficient levels we find, to between 60 and 100ng/ml during illness. Unfortunately locally this is not only not grasped, but also the vit D assay kit being used by private laboratories measures only total 25OHvit D level, not the needed active 25OH vit D3 level plus the potentially harmful (vitD receptor-blocking ) 25OHvit D2. This is a crucial omission which has been corrected by eg the Mayo Clini Lab, which routinely reports both D3 and D2 levels.

In the person not on vit D supplements, the mediocre ie insufficient total vit D level may mask that the crucial vit D3 level is actually seriously low- deficient. In the person on vigorous vit D2 supplement (the spuriously named “strong calciferol” 50 000iu tab no longer prescribed in USA but commonly in RSA, that neglects to state it is D2 not D3), the total 25OH vit D assay will be even more misleading if the level is well up, without the unwary being informed that it is harmful D2 that is elevated, and blocking the needed vit D3 level that the D2 is suppressing.

15 June 2014 CRUCIAL EFFECTIVE VITAMIN D3 DOSING: A major new metaanalysis of the benefit ofVitamin D3 and RespiratoryTractInfections RTIin PLOS 2013 at Sweden’s Karolinska Institute Bergman ea showed that in the 11 relevant trials (published between 2007 and 2012 ie done through the first decade of this century) using vit D3, “Overall, vitamin D showed a protective effect against RTI (OR, 0.64; 95% CI, 0.49 to 0.84). And the average vit D level at baseline was only 24ng/ml, but with the mediocre vit D3 doses used then of average 2000iu/d (300 – 4000iu/day) given for between 7wks and 3 yrs, the average bloodlevel achieved on replacement was only 50% higher at 36ng/ml”.

This confirms more direct experience with higher doses that blood level increment, and benefit, is proportionate to vit D3 dose, at least up to the proven speculative safe upper dose of at least 10 000iu/day (whereas the proven safe longterm daily dose is up to 50 000iu/day). “More important, the protective effect was larger in studies using once-daily dosing compared to eg monthly bolus doses (OR=0.51 vs OR=0.86, p=0.01)”. This concurs with our experience of major benefit against respiratory infection that is based on published studies giving a loading month’s dose of about 80-100 iu/kg/day ie ~3000iu/kg; then that monthly dose split conservatively eg 50 000iu every week or two depending on mass, and severity of ill-health; to a more successful blood-level of 60 to 100ng/ml.

These recent studies force us to conclude that bad weather, and bad prevalent respiratory viruses, and especially with major acute, or chronic illness as in those with or at risk of serious infections eg major trauma or sepsis, MERS-CoV, Ebola, malaria, cholera, cancer, diabetics, smokers, asthmatics, bronchitics, AIDS-TB., pneumonia and old age sufferers, and especially hospital, laboratory and clinic- health workers- we should give a loading dose of about 4000iu/kg, then 10 000 iu/d for an average 70kg adult, or 50 000iu every 5 days, or more simply 75000iu (about 1.5ml of 100cws vit D3 powder) weekly; or at a stretch, 300000 if not 400 000iu monthly. . As the common imported powder concentrate is 100 000 iu / Gm ie per 2 ml, it is simple to take the slightly sweetish powder up to 2 or more 4 ml teaspoons ie 200 000 -400 000 iu on the tongue.

The majority of residents of developed countries now live urbanised with mechanized transport, do not live and work / walk all day stripped in the sun. The poor malnourished peasants live crowded in ghettoes , and the poorest are generally the darkest skinned and therefore make the least vitamin D3. So with rare exceptions, everyone needs the vigorous vitamin D 3 doses discussed above.

But at the prevalent bulk vit D3 powder price of at most about $0,o2 per 100 ooo iu, at a mean population age of around 20 to 25 yrs -outside Europe- it would cost a country of eg 50 million people perhaps $o.5 per head per year ie conservatively $25 million a year to prevent > 90% of common illnesses including drugging and violence consequences. Of course no government can tolerate such massive loss of jobs and taxes in a decimated disease industry that turns over $ trillions annually – up to 18 % of national budgets. So it’s up to individual adults, especially householders, educators and employees , to see that the cheapest cure- all after clean water – vitamin D3 – is recommended and freely available.

We health professionals with our highly vulnerable populations in South Africa and worldwide (epidemic/endemic HIV, TB, cancer, drug addiction, MERS-CoV, asthma, diabetes, cardiovascular, malnutrition, alcoholism and violence) therefore surely have no choice but to swop promptly from prescribing vit D2 “Strong Calciferol” (a dangerous misnomer) to prescribing vitamin D3 at vigorous dose (with if possible occasional blood level check of 25OHvit D3)- at a trivial imported and distributed cost (100cws) to South African state clinics of perhaps<1/4 of the cost of D2 eg R1 per patient per month for a conservative 100 000iu monthly (ie after an appropriate germicidal loading dose of eg 3000 iu/kg) if not the more realistic dose double that- still at only eg US$0.2 a month.

Health Authorities everywhere have an obligation to enforce the use of vitamin D3 and not vitamin D2 globally ..

Queries and rebuttals all over the world are questioning the negative French (Autier ea) Vitamin D status and ill health: a systematic review published last month by the UK Lancet Low serum concentrations of 25-hydroxyvitamin D (25[OH]D) have been associated with many non-skeletal disorders. However, whether low 25(OH)D is the cause or result of ill health is not known. We did a systematic search of prospective and intervention studies that assessed the effect of 25(OH)D concentrations on non-skeletal health outcomes in individuals aged 18 years or older. We identified 290 prospective cohort studies (279 on disease occurrence or mortality, and 11 on cancer characteristics or survival), and 172 randomised trials of major health outcomes and of physiological parameters related to disease risk or inflammatory status. Investigators of most prospective studies reported moderate to strong inverse associations between 25(OH)D concentrations and cardiovascular diseases, serum lipid concentrations, inflammation, glucose metabolism disorders, weight gain, infectious diseases, multiple sclerosis, mood disorders, declining cognitive function, impaired physical functioning, and all-cause mortality. High 25(OH)D concentrations were not associated with a lower risk of cancer, except colorectal cancer. Results from intervention studies did not show an effect of vitamin D supplementation on disease occurrence, including colorectal cancer. In 34 intervention studies including 2805 individuals with mean 25(OH)D concentration lower than 50 nmol/L at baseline supplementation with 50 μg per day or more did not show better results. Supplementation in elderly people (mainly women) with 20 μg vitamin D per day seemed to slightly reduce all-cause mortality. The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status is reported in a wide range of disorders. In elderly people, restoration of vitamin D deficits due to ageing and lifestyle changes induced by ill health could explain why low-dose supplementation leads to slight gains in survival.

Ongoing randomised clinical trials assessing the ability of vitamin D supplementation to reduce the risk of several non-skeletal disorders involve a population larger than that of Cambridge, UK, and will cost millions of research dollars. VITAL, for example, will enroll 20 000 participants and has US$22 million in funding. This vast investment of effort by patients, researchers, and funders is laudable, as it is almost certain that it will be sufficient to answer a question that has long kept the medical community in the dark.

Vitamin D first became a medical success story when its importance in bone health and calcium homoeostasis was proven decades ago. Since then, epidemiological evidence has been accumulating to support a role for vitamin D in the protection of individuals from various non-skeletal disorders including cancer, cardiovascular diseases, autoimmune and inflammatory diseases, dementia, and diabetes; it might also reduce all- cause mortality. Many of these studies show a strong association between low vitamin D concentrations anddisease. However, the results of myriad recent small randomised controlled trials are almost unanimous in concluding that vitamin D supplementation provides protection from few, if any, of these outcomes.

Vitamin D is a steroid hormone with pleiotropic and tissue-specific effects owing to the wide expression of the nuclear vitamin D receptor in many different tissues,and the many genes that are targeted by its actions. In the skeletal system, vitamin D promotes healthy development and remodelling of bone. In other tissues, vitamin D is postulated to mediate potentially beneficial effects via a wide variety of mechanisms: some evidence suggests that it exerts anticancer activity by limiting hyperproliferation of certain cell types, that it promotesmetabolic health by regulating lipid metabolism in adipocytes, and that it limits autoimmunity bysuppressing inappropriate immune responses. In a systematic review in The Lancet Diabetes & Endocrinology editorial , Philippe Autier and colleagues discuss a large number of observational studies suggesting That high serum concentrations of vitamin D might be protective.

For example, those with high vitamin D had decreased risk of cardiovascular events by up to 58%), diabetes (by up to 38%), colorectal cancer (by up to 33%), and all-cause mortality (by up to 29%). However, they also compare these findings with the results of randomised clinical trials, which reveal a very different picture: no reduction in risk was found, even in trials involving adequate supplementation of participants with lowvitamin D levels at baseline (less than 50 nmol/L). Autier and colleagues also did a new meta-analysis of 16 trials that assessed the effects of vitamin D supplementation on blood HbA1c, a biomarker mainly used for monitoring disorders of glucose metabolism.

Although type 2 diabetes is associated with low vitamin D, the results show that vitamin D supplementation does not reduce HbA1c

. Thus, it looks increasingly likely that low vitamin D is not a cause but a consequence of ill health.

Despite the growing body of evidence indicating that vitamin D is unlikely to prevent non-skeletal disorders, there is strong support for its use from many prominent members of the research community, which is fuelled by the relatively low toxicity of vitamin D, the glimmer of positivity from some trials,and the large body of evidence from prospective observational studies. For those who ‘believe’, the lack of benefi t found in most trials completed thus far can be attributed to issues including inadequate supplementation, testing of a population not sufficiently vitamin D deficient at baseline, incorrect

formulation, underpowering, or insufficient follow-up. Vitamin D might not be safe in all settings, however.

Supplementing at high doses could cause harm in people with already high concentrations of serum vitamin D, particularly in those with liver, kidney, or vascular problems. This is a concern, given the large number of people taking vitamin D supplements (up to 50% of adults in the USA).

Large clinical trials to assess the effects of vitamin D on non-skeletal health outcomes are therefore justified. It would be a real boon to patients if the results are positive, but unless effect sizes for clinically important outcomes are large, the results will only confirm the neutral effect reported by most clinical trials thus far. Although this investment might therefore have little effect on current guidelines, the results will at least allow the research community to move on.

This French review of Vitamin D is the sort of tactic regularly concocted by Big Pharma and the Disease Industry for the media, to discourage patients and doctors from taking/prescribing effective doses of supplements (beyond a lowdose multivite a day), instead force them to take Big Pharma poisons- synthetic new risky designer drugs- like antibiotics, antipain, anticancer, anticholesterol, antiosteoporosis, antiplatelet,antihypertensive, vaccines, antiflu, – to make massive profits for the Disease Industry, but not address or cure the deficiency causes of disease. At the behest of Big Pharma like Roche, their lobbyists the FDA, the European Medicines Authority and the UK NHS are trying to push through legislation that will make anything but lowdose multisupplements available to the public solely on doctors’ prescription.

Meanwhile, Big Pharma companies are paying fines of over $10 billion a year for promoting their snakeoil prescription designer drugs by fraud, when these drugs are allowed to be registered for chronic use after small trials of only 6 to 12 weeks, and the researchers who publish the trials for megadollar fees are regularly caught out, fired but rarely jailed. …… The Big Pharma guys simply bill the cost of the fines into their marketing expenses- their bosses, and the politicians they buy off, are too big to jail… Regulators then allow the drugs to be prescribed for years until enough patients sicken and die for there to be an uproar and cancellation- as happened recently with Prot(e)os the synthetic ranelate ‘osteoporosis’ snakeoil;. Now a top Dutch researcher has been fired for falsifying trials to promote betablockers for hypertension – when these have been discredited as routine therapy for this purpose for over a decade.

yet the Regulators led by the FDA – which is massively funded solely by Big Pharma as their ally- insists that vitamins, minerals and other long-proven natural supplement therapeutics, prime human hormones like melatonin and physiological human sexhormone creams , have to undergo $multimillion trials before they can be marketed as already long-evident safe effective therapies.

none of the vit D trials used the dose of vit D3 now recommended on solid evidence that we should all take – 80 (to 100)iu/kg/day or 2400-3000iu/kg/month of vitamin D3- ie about 150 000 – 200 000 iu to start and then per month for average adults – to maintain healthy 25OH vit D levels around 60-100ng/m (here our bloodlevels are usually between 10 and 20 ! because we take little dairy products, nuts and sunshine- we cover up and live indoors.) .

Most of the reported trials used only about 5% of the recommended vit D dose ie ~200 to 400iu/day ie 6 iu/kg/day! this dose does nothing except partly prevent rickets- in infants! Pregnant women are still routinely given such weak near-nonsensical doses of vit D.

and as Cannell’s review of the Autier analysis points out, the vitamin D trials trials under way – * in USA-Boston VITAL study 20 000pts) , Finland (FIND 18000 pts and UK(VIDAL1600pts ) , in some 40 000 subjects, due for publication only between 2017-2020- are using only 1600 to 3200iu vit D a day or about 48 000 to 96000iu/month ie perhaps 32iu (25 to 40) /kg/day. So they are testing still modest doses and blood level targets. .

ideally you should check your 25OH vit D and calcium levels to make sure you are on the right dose- but always taking some magnesia supplement, and at least 2 liter of water/ sodawater/clear fluid a day to avoid dehydration, kidney stones and vascular disease (which highdose calcium supplement eg 1000mg & vit D3 400iu/day cause).

8 April 2013 UPDATE: VITAMIN D3 THE AMAZING SUPPLEMENT

It is sad to record that Dr Walter Stumpf died suddenly a few months ago during ongoing correspondence. The world has lost a teacher of the century in both biological sciences and the humanities, metaphysics and philosophy,..

This week – as flu mushrooms in the southern hemisphere autumn- the Canadian Medical Association Journal April 3-8 features early-release articles on concerns about the Asian flu viruses and especially the SARS-nCorVirus. Is mass vaccination the answer? or did this in fact worsen mortality in previous North American epidemics of eg H1N1? which brings us back to global protection against infections and all major diseases with lowcost safe VitaminD3 at say 50 000iu(~700iu/kg)/week plus the other all-system protective supplements – eg multivitamins (especially vit C and K) and minerals especially magnesium, zinc, idine and selenium; and during epidemic times, major daily boost in vits D3 and C.

In December 2012 the University of San Diego published a useful researched update on vitamin D3 and breast cancer; pointing out again that while the increase in benefit obviously drops off with increasing dose, safe dose is up to at least 10 000iu a day or 70 000iu a week, to a bloodlevel around 100ng/ml; and toxic dose requires at least 40 000 iu a day chronically (if not 600 000iu/d as other evidence suggests). The projections for breast cancer reduction fit with the same team’s predictions in 2007.

So apart from maintaining good water intake, and avoiding taking ill-advised unbalanced solo calcium supplement, for optimal dosing in those with cancer or any other high risk, blood levels of both 25hydroxy vit D3, 1,25 calciferol, calcium, phosphate and creatinine, should be monitored occasionally, to avoid the rare risk of kidney stones and arterial/breast calcinosis.

Remember that magnesia, phosphate and vitamin C and K2 supplements are amongst the most important of at least 40 to accompany vitamin D3.

Last month three new studies affirmed the importance of vigorous vitamin D3 levels for genetic, heart and all health.

Holick’s group at Boston University show the profound .Influence of vitamin d status and vitamin d3 supplementation on genome wide expression of white blood cells. No studies have reported on how vitamin D status and vitamin D3 supplementation affects broad gene expression in humans. A randomized, double-blind, single center pilot trial was conducted for comparing vitamin D supplementation with either 400 IUs (n = 3) or 2000 IUs (n = 5) vitamin D3 daily for 2 months on broad gene expression in the white blood cells collected from 8 healthy adults. in the winter. CONCLUSION SIGNIFICANCE: Our data suggest that any improvement in vitamin D status will significantly affect expression of genes that have a wide variety of biologic functions of more than 160 pathways linked to cancer, autoimmune disorders and cardiovascular disease with have been associated with vitamin D deficiency. This study reveals for the first time molecular finger prints that help explain the nonskeletal health benefits of vitamin D

The magnitude of vitamin D inputs in individuals not taking supplements is unknown.. they reanalyzed 3000 subjects’ individual 25(OH)D concentration data from 8 studies involving vitD3 supplement. The total basal input (food plus solar) was calculated to range from a low of 778 iu/d in patients with end-stage renal disease to a high of 2667 iu/d in healthy Caucasian adults. Consistent with expectations, obese individuals had lower baseline, unsupplemented 25(OH)D concentrations and a smaller response to supplements. Similarly, African Americans had both lower baseline concentrations and lower calculated basal, all-source inputs. Seasonal oscillation in 4 studies ranged from 5.20 to 11.4 nmol/L, reflecting a mean cutaneous synthesis of cholecalciferol ranging from 209 to 651 iu/d at the summer peak. We conclude that: 1) all-source, basal vitamin D inputs are approximately an order of magnitude higher than can be explained by traditional food sources; 2) cutaneous, solar input in these cohorts accounts for only 10-25% of unsupplemented input at the summer peak; and 3) the remainder must come from undocumented food sources, possibly in part as preformed 25(OH).

August 2009 SUMMARY: Evidence is overwhelming that the prime sun-induced steroid hormone Vitamin D3 cholecalciferol – soltriol- is invaluable in 20fold higher dose ie perhaps 5000 to 10 000iu/day rather than has been preached to date (200- 400iu/d), as part of lifelong hormone replacement HRT to prevent all major chronic degenerative diseases in all humans living and working indoors. Effective dose of vitamin D3 supplement can reduce deathrate and disease by an astonishing 20%- that is indeed a panacea almost as good as other natural micronutrient supplements eg fish oil, metformin, and appropriate sex hormone replacement SHRT. It is becoming clear that with rare exceptions everyone- especially those with serious disease eg cancer, heart, lung, brain, nerve/muscle/bone/joint or inflammatory bowel diseases or chronic infections like TB HIV influenza or human papilloma virus – should take a daily supplement of about 10 000iu (1/4 mg) vitamin D for as little as ~ R10 US$1 a month ; ideally under supervision of some health professional. All that is required is occasional check of blood chemistry, and good diet and fluid intake.

And obviously because of vitamin D3’s benefits in lowering all diseases, when using vigorous dose vitamin D, one must expect to need to lower prescription drug treatments for diabetes, hypertension, depression, heart disease, lung disease, arthritis, infections etc as these ailments improve from the vitamin D replacement over months.

This review is especially appropriate on our Womens’ Day 9 August 2009 for a natural product so important for the health of women , that commemorates the year 1956 when 20 000 women marched in defiance of male despots’ fascist apartheid pass laws. The ages-old discrimination against women is epitomized by the pragmatic liberal economist Professor Ken Galbraith’s lecture to the Royal Society of Medicine in 1973 on the problem of unequal development and centralization of power in male technostructure – profit maximization.

No-where in business is this better shown than in Big Business creating demand by saturation marketing, including the medicalization of health. This involves disease-mongering through creating unnecessary concerns so as to expand markets among the well for patents eg blanket cholesterol or mammography or colonoscopy screening, or remedies for eg female arousal disorder, anxiety, reactive depression, mild-to-moderate hypercholesterolemia – when very few have been proven to need or benefit from such labels, procedures and drugs.

VITAMIN D3 SOLTRIOL : INFORMATION EXPLOSION:

The first of 46200 entries on Medline on vitamin D is from Oxford by Heaton 1922 . There are 272 500 entries on vitamins since 1918, the first specific one by Jack Drummond in 192o, but of course vitamin D was first identified by Mellanby 1919, preceded by vits A, B1 and C between 1909 and 1912. From a recent historical review (table 1) of hormones, vitamin D3 was perhaps the 7th hormone recognized after testosterone and estrogen (China 2600 years ago) , thyroid (1891) epinephrine secretin parathyroid and antidiuretic hormone.

Soltriolis an exquisite description for a sun-activated steroid, the cardinal prohormone vitamin D3 made from cholesterol via sunlight exposure. Soltriol is not in a 1964 Oxford Dictionary, nor is it’s etymology detectable on Google search; it was indeed invented by the pioneer polymath neurologist Dr Walter Stumpf . On Medline search for soltriol, the first result is Corradino 1973…

It is intriguing to read that Dr Stumpf graduated in medicine in 1952- and 50 years later in 2005 he wrote on his website: “From the microautoradiographic target recognition and related actions it follows that vitamin D has healing potential for prevention and treatment of various deficiencies and ailments, including old age: a PANACEA? If there is any compound that deserves being designated a panacea, the multifunctional heliogenic vitamin D appears a suitable candidate. Philosophical consideration: “Vitamin D”, the term does not reflect its significance. I have used instead SOLTRIOL in several publications as a more appropriate designation. – Is there not a link to Heraclitus emanation of “ ever-living fire ”? The cosmic solar fire (Soltriol) as the sustaining life force, providing wave length energies for Temperature, Visible Light , and Ultraviolet B “. ” The Main Biological Role of Vitamin D is Seasonal Adjustment of Vital Functions: These include regulation of growth, reproduction, survival stress response; endocrine and exocrine secretion, cell proliferation, cognition and mood; neuro-motor, neuro-endocrine, and neuro-sensory functions, immune response, cardio-vascular and gastro-intestinal functions, regulation of calcium and other mineral levels, cell proliferation and protein synthesis-differentiation.

Considering the decades of vitamin D use for its other benefits, it is ironic that a 1999 University California website on The History of Vitamin D has never been updated to cover more than the anti-rickets protection from vitamin D. But as Prof Stumpf writes to me today, ultimately it is the sun that is the panacea, transmitting it’s healing powers via the skin-activated messenger hormone vitamin D.

It is now almost a year since this column last reviewed vitamin D3’s benefits against all major diseases (see table) – during which year scores of new randomized controlled trials RCTs of vitamin D have appeared- there are now some 1680 RCTs on it since 1965. Carpenter 1999 reviews Forgotten Mysteries in the History of Vitamin D.

Women have a raw deal: due to their prime role and innate sense for survival of the species, for nuturing and caring, they live about 10% longer than their mates, but as a result endure far more illness, as well as assault, disability and murder (mostly inflicted by the careless male).

PROTEAN STEROIDS, PROTEAN FUNCTIONS: Calcitriol is one of many human steroids that include the sex hormones, aldosterne and digoxin; as well as nonhuman steroids which also have important medicinal use- like phytosteroids, equine steroids like the equilins eg premarin, and the important ecdysteroids in insects and some plants. Stumpf has again stressed the wide distribution in humans of vitamin D receptors VDRs, indicating their importance in protean human functions far beyond calcium regulation.

VITAMIN D AND ALL-CAUSE MORTALITY:it is just a year since Melamed ea from USA showed that having low vitamin D (as opposed to high level) increases all-cause mortality by 26%- thus taking submaximum safe dose of vitamin D can improve chance of survival by about 20%. This for as little as R10/month – $1- in South Africa.

In 2000, the Seven Country Study Group showed that ” saturated fat,vitamin C and smoking are the major determinants of all-causemortality at the population level” ie the higher the fat and smoking intake and the lower the vitamin C, the higher the deathrate. We now know better- serious vitamin D deficiency joins the list, which of course includes alcoholism. .

VITAMIN D AND CARDIOVASCULAR DISEASE CVD

Pizzorno 2009 reviews the strong evidence of the importance of balanced vitamins A D and K supplements in reversing the epidemics of both CVD and osteoporosis.

VITAMIN D AND DEPRESSIVE/NEURODEGENERATIVE DISEASE

over 20 articles already this year attest to the importance of vigorous vitamin D levels in reducing these diseases.

The much higher incidence of autoimmune diseases in women – especially SLE systemic lupus erythematosis and RA rheumatoid arthritis- let alone far higher younger female risk for fractures- must have been obvious for millennia. So obviously genetic female factors play a major role in these diseases – now surely attributable largely to the reproductively necessary absence of the Y chromosome, and thus the 100fold lower testosterone: estradiol T:E2 ratio in women (perhaps 2:1) than in men (in youth, >200:1).. It is common cause that estrogen is immunostimulant whereas testosterone and progesterone (like vitamin D) are immunomodulating. Hence testosterone and progesterone levels soar during pregnancy to prevent the mother rejecting her foetus. This partly also explains why vigorous vitamin D supplement also greatly improves fertility and pregnancy outcome.

VITAMIN D AND RHEUMATOID ARTHRITIS: many studies show the benefits of the prime anabolic steroids- vitamin D and androgen (Devis 1950) supplements- in treatment of all inflammatory disease, especially when inflammation itself weakens bone and all other tissues. The latest – last month (Chabchoub 2009)- shows “a possible role for XCI mosaicism in the pathogenesis of RA and thyroid disease and may in part explain the female preponderance of these diseases”. But the first and only randomized controlled trial of the effect of vitamin D on modifying RA appears in 1973 (Brohult) and the only open trial (Andjelkovic 1999) in RA showed that “alphacalcidiol is a powerful immunomodulatory agent with fairly low hypercalcemic activity”.

VITAMIN D INTOXICATION: The low toxicity of vitamin D3 is fortunate because while it is ideal to monitor vitamin D levels on effective replacement, the blood test costs about R660- $80- locally; hence all one needs to do is exclude kidney problems (which may need even higher dose of vitamin D3), and risk of kidney stones- but perhaps checking blood calcium and creatinine at baseline and occasionally, and ensuring balanced supplement of calcium-magnesium – boron-zinc-manganese-(iron if deficient) and vitamins B, C, D and K. Since vitamin D intoxication (toxic rise in blood calcium- hypercalcemia) in some opinions requires ~>600 000iu/day for months, ths is inconceivable unless one were to swallow say twelve 50 000iu vitamin D every day for months. So the only recognized form of vitamin D intoxication could be an industrial accident involving mistaken use of vitamin D concentrate in medicine.

HYPERCALCEMIA HIGH BLOOD CALCIUM: medical causes are rare without gross calcium overdose (milk alkali syndrome) or other specific symptomatic diseases – eg primary hyperparathyroidism, sarcoidosis, tuberculosis, and lymphoma.And fortunately most patients with these diseases and hypercalcemia are far more likely to benefit from therapeutic treatment with vitamin D than worsen on it.

OVERDOSE: HYPERVITAMINOSIS D: WIKI says “Vitamin D stored in the human body as calcidiol (25-hydroxy-vitamin D) has a half-life of about 20 to 29 days.[17] Ordinarily, the synthesis of bioactive vitamin D hormone is tightly regulated, and prevalent thinking is that vitamin D toxicity usually occurs only if excessive doses (prescription forms or rodenticide[38] . Serum levels of calcidiol (25-hydroxy-vitamin D) are typically used to diagnose vitamin D overdose. In healthy individuals, calcidiol levels are normally between 32 to 70 ng/mL (80 to 175 nmol/L), but these levels may be as much as 15-fold greater in cases of vitamin D toxicity. Serum levels of bioactive vitamin D hormone (1,25(OH2)D) are usually normal in cases of vitamin D overdose. Symptoms include Dehydration Vomiting Decreased appetite (anorexia) Irritability Constipation Fatigue.

Overdose of vit D3 has been observed at 1925 µg/d (77,000 IU per day). Acute overdose requires between 600,000 and 1,680,000 IU per day over a period of several days to months, with a safe intake level being 10,000 IU per day.

A 2007 risk assessment suggested that 250 micrograms/day (10,000 IU) in healthy adults should be adopted as the tolerable upper limit.[39]In adults, sustained intake of 100,000 IU can produce toxicity within a few months.[2]For infants (birth to 12 months) the tolerable UL is set at 1000 IU, and 40,000 IU has been shown to produce toxicity within 1 to 4 months. All known cases of vitamin D toxicity with hypercalcemia have involved intake of or over 40,000 IU)[42].

Although normal food and pill vitamin D concentration levels are far too low to be toxic in adults, people taking multiples of the normal dose of codliver oil may reach toxic levels of vitamin A, not vitamin D, [43] if taken in an attempt to increase the levels of vitamin D. Most officially-recorded historical cases of vitamin D overdose have occurred due to manufacturing and industrial accidents.[42]

Some symptoms of vitamin D toxicity are a result of hypercalcemia caused by increased intestinal calcium absorption. Vitamin D toxicity is known to be a cause of high blood pressure.[45] Gastrointestinal symptoms of vitamin D toxicity can include anorexia, nausea, and vomiting. These symptoms are often followed by polyuria (excessive production of urine), polydipsia (increased thirst), weakness, nervousness, pruritus (itch), and eventually renal failure. Other signals of kidney disease including elevated protein levels in the urine, urinary casts, and a build up of wastes in the blood stream can also develop.[2] In one study, hypercalciuria and bone loss occurred in four patients with documented vitamin D toxicity.[46] Another study showed elevated risk of ischaemic heart disease when 25D was above 89 ng/mL.[47] Vitamin D toxicity is treated by discontinuing vitamin D supplementation, and restricting calcium intake. If the toxicity is severe blood calcium levels can be further reduced with corticosteroids or bisphosphonates. In some cases kidney damage may be irreversible.[2]

Exposure to sunlight for extended periods of time does not normally cause vitamin D toxicity.[42] This is because within about 20 minutes of ultraviolet exposure in light skinned individuals (3–6 times longer for pigmented skin) the concentration of vitamin D precursors produced in the skin reach an equilibrium, and any further vitamin D that is produced is degraded.[48]Maximum endogenous production with full body exposure to sunlight is 250 µg (10,000 IU) per day.[42]”

VITAMIN D AND SEX:

Biologically, the most imperative function for species survival is sex- reproduction. Vitamin D is clearly a potent anabolic reproductive steroid like testosterone: The first paper on this association on Pubmed appears in 1963 from Russia (Gokinaeva).

Mirzahossein in 1996 showed that,” given in the critical period of foetal imprinting, vitamin D may influence steroid hormone-receptor commanded events for life in a way similar to synthetic steroid hormone analogues”. So as with marine omega3., it is crucial that future parents take enough vitamin D.

Friedrich 2002 showed that even prostate, colon and normal cervical tissue and cervical cancer cells have VDRs – vit D receptors- and may be new targets for cancer prevention or cancer treatment.

VITAMIN D AND SLE- SYSTEMIC LUPUS ERYTHEMATOSIS: on medline the first reference to immunosuppression with vitamin D was by Bourdial 1963 on nasal allergy, and the first for vitamin D and immunomodulation is by Nagler & Pollack 1986.:

However, the first paper on the importance of Vitamin D3 deficiency in SLE appeared in Germany 1963, but the first paper in English and from an English country only in 1979 (O’Regan).

The focus throughout has been on the benefit of vitamin D in reversing the hyperimmunity of SLE, but of course vitamin D is equally important in preventing both the osteoporosis of inflammation, the fracture and wasting risks of cortisone treatment, and the vascular disease associated with SLE. In the last year alone there have been 10 such SLE – vitamin D major studies – 7 from the Americas and 3 from Europe.

SLE as well as plain lupus of the skin are generally regarded as disease that requires protection from the sun.

Now this week Wright 2009 shows that in children, SLE is associated with vitamin D deficiency, particularly among those subjects with SLE who are overweight.

VITAMIN D, SUNLIGHT, SLE AND CANCER:

The first case of SLE associated with cancer ( meningioma and cervix)- is reported by Williams 1956. The latest – last month- highlights increased risk of lymphoma, cervix and bronchus cancers.

Search for malignant melanoma MM and SLE finds the first reference in 1963. yet most of the papers are about reactions to interferon therapy, or immune markers- there is one solitary case report (1991 Sulkes, Israel) of a patient with indolent SLE who after 15 years developed and died of rapidly spread of MM. These authors comment on the infrequent association of SLE & solid cancers, the commonest being uterus and bladder.

So it is exciting that while more sun exposure causes skin cancer and especially cutaneous melanoma CMM, (Tuohimaa 2007), sun exposure also improves survival from CMM- and from a wide range of internal cancers – (especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder and kidney cancers). This favourable effect of more sunshine is obvious when comparing the lower cancer and heart disease deathrates in sunnier southern versus the darker northern countries. Only rare skin diseases eg porphyria cutanea tarda are contraindications to sun exposure of the skin. But at least one study Holme 2008 shows vitamin D deficiency in erythropoetic porphyria.

Professor Halstead 2008 (and many others) conclude that the high fructose corn syrup routinely used in fast foods and cooldrinks in first-world manufacturing is rapidly increasing obesity, lipidemia (and metabolic syndrome and cancer); while folic acid food fortification is causing low B12 levels and thus possibly increasing dementia, vascular disease and advanced precancerous colorectal adenomas and breast cancer. This trend is aggravated by at least three scientifically unvalidated obsessions of Regulators and the Medical hierarchy:

1. low diet cholesterol in those with mild to moderate cholesterolemia;

Protection from both cancers and SLE is probably associated with higher vitamin D level above ~100nmol/L. Both lupus and cancers are due to altered immunity. But SLE is due to increased autoimmunity- hence cancers are infrequent during active SLE; whereas cancers are due to reduced immunity – hence are associated with immune suppression, whether by cortisone (including stress) / chemotherapy, or deficiency of vitamin D – dietary and lack of sunshine..

While there is no clear overall relationship of statins to osteoporosis or cancer, Kunitomo 1989showed that cholesterol reduces and corticosteroids enhance the toxicity of vitamin D in rats. Montagnani 1994 showed that pravastain does not interfere with the circulating levels of the main vitamin D metabolites.

VITAMIN D AND INFECTION:

For an acute infection, Cannell and Hollis 2008 suggest vitamin D in an antimicrobial dose of 2000iu/kg eg 120 000 iu a day for 3 days- to produce enough of the naturally occuring antibiotic cathilicidin. Ginde 2009 show that those with high vitamin D levels have less respiratory infections. This column has previously reviewed the dramatic benefits of vitamin D on infection mortality in AIDs- TB patients. Obviously one is going to be cautious pushing vitamin D in a patient with known kidney stones, or hypercalcemia.

VITAMIN D : WHY THE INCREASING DEFICIENCY, NEED FOR SUPPLEMENT ?

Never mind the poor and chronically ill, the aging especially need much more vitamin D, and benefit the most. Even in a sunny fishing nation like Spain, elderly women do not get enough vitamin D from fish or other foods, and most have suboptimal blood levels of it.

Apart from dietary intolerance and obsession reducing intake of cholesterol and dairy products, the vitamins and minerals in particular have been greatly depleted and imbalanced in commercially produced- and especially genetically-modified food. And while increasing longevity, food scarcity -poverty and mushrooming prices (cartel pricefixing that is ignored by well-paid politicians and regulators) – are prime causes, Politicians and Regulators have worsened this by falling decades behind in ignoring the leading 20th pioneer nutritionist/ economists like the USA’s Professors Linus Pauling the unique double Nobel prizewinner prophet of vitamin C and peace; Ken Galbraith; and the UK’s SirJack Drummond. The latter two respectively brought the Allies (under FD Rooseveld and WS Churchill) through WW2 by putting farming- healthy food production and pricing- as the painfully obvious priority- which selfserving gluttonous politicians like Nixon, Bush, Kissinger, Mugabe and Mbeki, and most others leaders (who support, not just tolerate such despots) simply ignore since they detest “surplus people”- the honest poor; if not also hardworking farmers.

It is no coincidence that Pauling and Galbraith both graduated from agricultural colleges. And no coincidence that all three nutritionists were the targets of politician-business moguls because of the obstacles they posed to the profiteering national economic sabotage that is the lifeblood of ruthless businessmen-capitalists from before Nixon- Connolly- Reagan- Kissinger and Thatcher, through to the Bushes and Blair and Montsano-GD Searle, Mbeki and Zuma, and the arms, oil, banking, mining, media, food, sex, tobacco-alcohol and medical-big pharma industry mafiosi cartel who make or break presidents and governments.

James Ferguson makes a strong case for The Vitamin Murders, that Drummond (and his family) were butchered in a Vitamin Industry contract in France as a lesson to do-gooders because his advocacy of the primary role of good natural nutrition and vitamins was such an obstacle to the fast food and synthetic drug industry. Conspiracy theorists could argue that, like Pauling’s vitamin C, the Drug Industry have through the FDA managed to ensure that only this year is the FDA grudgingly moving to raise the Recommended daily Allowances of vitamin D (and C) even fractionally above the present rickets- (and scurvy) preventing doses, as opposed to their modest 25 to 50fold fold higher intakes that have been known already for decades to be both safe and major benefit against all diseases.

John Le Carre’s The Constant Gardner echoes that ongoing conspiracy scenario, the battle between Big Pharma with it’s drug lobbyists (including the USA FDA and the European Union’s European Medicine’s Authority, and leading politicians) to promote their lucrative modern synthetic chronic drugs (none of which have been shown to reduce all-cause disease and mortality as do natural supplements), versus nutritionists and informed consumers who know that broad natural supplements (vigorous vitamins, minerals and biologicals) to bolster the failing adulterated food chain are more important and effective than any patented designer drugs in combating all disease. Unfortunately the necessary advocacy for natural supplements has been muddied by fraudsters like the Big Pharma- FDA- academia cartel (who swamp the medical literature with trial and review papers favouring their snake oils), the Rath Foundation, and our local dissidents against reason like Mbeki, and Drs Manto Tshabalala-Msimang, Nkosasama Zuma and Olive Shishana.

CONCLUSION: In 2006 Dr Walter Stumpf in THE DOSE MAKES THE MEDICINE wrote: “in recent years, discussion raged about the negative effects of estrogen-replacement therapy and its relationship to cancer. In numerous articles, the side-effects of estrogen treatment were highlighted in a generalized fashion and, although consideration was given to the duration of treatment, the relationships to dose (let alone type and route of estrogen) were frequently left out. And yet, considerations of dose and time in pharmacology and toxicology are paramount.
Similarly, awareness of proper dosage is crucial to the development of future vitamin D therapies. Physiologic dosing of vitamin D does not cause hypercalcemia – hypercalcemia is related to overdosing ie closer to 100 000iu/day. Considering the many target tissues that are unrelated to systemic calcium regulation, most therapeutic effects of vitamin D occur independently of the high-dose systemic calcium effects. Because of the biased focus on calcium, the many other effects tend to remain unnoticed and hidden. Future research needs to give more consideration to dose-effect relationships by monitoring target functions independently of systemic calcium regulation.
New therapeutic applications of vitamin D can be established for cardiovascular, neurological, endocrine, immune, gastrointestinal, reproductive and other diseases, including posttraumatic and gerontological deficiencies, in which the polyfunctional effects of the hormone not only come to bear, but can also be controlled and maximized for optimal health.”

Since the global population shift from rural to city life and work the past century ie in our lifetispan, humans have largely gone from being healthy longlived outdoor food-producing workers living on their own fresh produce including organically grown unadulterated fresh food and dairy products – or fish- (rich in micronutrients), to working mostly indoors and consuming largely micronutrient-depleted food as well as multiple noxious deliberate industrial pollutants- from sugar and alcohol to estrogenics, pesticides, heavy metals, cornsyrup and aspartamate.

Like fish oil is the most important food extract we have (and businessmen are ruthlessly harvesting to extinction), vitamin D3 has become the anti-disease vitamin of the past decade, joining vitamins C & B as the panacea vitamins that can and should be supplemented in far higher dose than anti-vitamin “Regulators” and professional researchers and associations (with vested interests in protecting their funder- Big Pharma) approve.

But as the more affluent age and increase in numbers, the micronutrients that deplete (with longevity, the deteriorating food chain, and unnecessary drugs),- especially vitamins K, chondroglucosamine, N-acetyl cysteine, alphalipoic acid, Co-Q10, arginine, carnitine, carnosine, riboseand the marine EPA and DHA- are fast becoming the “vitamins” of the next decade.

Tragically, edible marine products especially marine omega3 EPA+DHA are rapidly becoming so scarce that the vast majority of people can neither source nor afford the minimum optimal gram a day, until science breaks through to synthesize these uniquely beneficial free fatty acids. But at least the supply of minerals, and vitamins including D3, is inexhaustible and therefore freely available at reasonable cost.

ndb

dedicated to Dr Walter Stumpf, whose >300 papers (~24% on vitamin D) on Medline apparently span 1963 to 2008- on vitamin D the first in 1979, the last 30years later appropriately on Vitamin D and the digestive system. By comparison, Pubmed lists only 3 papers by Albright, in 1938-9.

For the disabled – by arrangement drive up the ramp to the Clinic door on the Grove Bldg 1st floor parking deck.

Under CMS Council for Med Schemes Reg 10(6), open Medical schemes eg hospital plans have to pay from their own funds (not members’ savings) for appropriate outpatient consultation (tariff item 0191) for PMBs ie major conditions eg cancer, depression, neck/spinal problems, serious heart, lung, other disease., etc. Breast and osteoporosis concerns are generally part of menopause consultations N95.9 (if not already eg breast cancer code C50) and thus are often billable med scheme benefits. The menopause billable item only applies if you are 45yrs upwards, unless you have had total hysterectomy.

On patients’ requests, appropriate invoice can be prepared and submitted to your scheme for refund of your due benefits. Some schemes eg hospital plans falsely deny due benefits until reported to their regulator CMS. For medical plans where the billable tariff benefit rate is higher than the breast screening fee paid, the med plan rate 0191 will be charged eg R790 by the contracted specialist, and refundable by Discovery to the member. some basic schemes eg Keycare, Bonitas require preauthorization, or referral by their contracted GP .

This is not scientific precision. This is not peer reviewed. This might not resist the rigor of an editor. These are simply observations intended to spur thought and look laterally.

Much advice about food appropriate for health has been given. Much of that has been based upon (often marginal) statistics. Many are deduced from self-reporting surveys. However the variables are so great that it is impossible to accommodate these into meaningful statistics. A few of these variables include quantum of food, types of mixtures of food, frequency of these foods, plus multiple variables related to micro-nutrients ingested simultaneously, and more.

When in doubt, it has been said, look in the instruction book. The instruction book for animals (including the human) exists in the animal. It is the inclination to eat some foods and the abhorrence of others.

Without the instruction book, one has to look at design specifications. Unfortunately the animal-machine-design did not consider the possibility of limitless food, or great food variety, or types of current cultivars. So selection by appetite might be flawed, and one is left guessing (somewhat) about the design specification. That is what is addressed here.

But before that, if one wants to live longer, the method has been (scientifically) available for the better part of a century. Simply, eat less. Eat less than your appetite drive. Eat less than your cohorts.

But let us look at design. Suppose humans were to be designed from scratch, which fuels (i.e. foods) should be selected, bearing in mind the limitations of availability, and knowing that the human is a mobile device with defined functional requirements and a limited life-span? Consider these options, and consider how they fit with current eating patterns:

Fat is probably the most desirable and quintessential food for humans. It is the supreme appetiser. It carries essential vitamins. Fat the highest calorific gain of all foodstuffs whilst it has a low energy cost for ingestion and digestion. It is the most cost effective source of energy. Yet fat has powerful negative feedback mechanisms. Therefore, although fat stimulates appetite it also produces satiation relatively rapidly. Rapid satiation allows food to be spread to the entire pack, in keeping with expectations of le milieu exterior which demands survival of the group, not the greedy individual. However the satiation of fat can be strongly altered by salt. Therefore, salted fat and perhaps salted protein can become “compulsive” foods, inducing the eater to keep eating until gorged. So we have yet another factor, the “additions” to food which induce compulsive feeding, prompted by those intent on making money out of food.

Protein is probably neutral tasting without the fat and salt, is not particularly palatable and does not have the “addictive” quality of carbohydrate. But it contains “essential” components which the human cannot manufacture, including amino-acids and vitamin C (curiously a “water-soluble” vitamin). It is also heavily mechanically bound to fat, and often inseparable.

Carbohydrate, on the other hand, was never particularly attractive to early humans. Yes, I know well enough that some carbohydrates, the sugary carbohydrates, are exceedingly attractive. But in primitive societies, all carbohydrates were not attractive. Pure sugar is a relatively new evolution. The current sweet fruits and even potatoes are the product of intentional selective breeding to make those carbohydrates more palatable.

The metabolisms of carbohydrate, the sugars, are again very different from fat, in that the same metabolic pathways are used for both the anabolism and the catabolism of carbohydrate. The control of carbohydrate metabolism lies outside the direct metabolic pathways, relying on end-organ control. These includes insulin receptors. This is distinct from fat where the anabolic and catabolic pathways are different, and so allowing feed-back to curb appetite and metabolic direction.

Carbohydrate’s prime quality is that it is cheap. As a consequence commerce has “wrapped” carbohydrate in both fats and sugar in order to make it compulsive eating at a cheap price. Amongst the most tempting ingestants are those that have both sugar and fat, as in chocolate.

Refined and manufacturer altered carbohydrate once ingested, prompt the desire to keep on eating it. Carbohydrate can have a long shelf life, is easily stored and so lends itself to easy snacking. No surprise that it is perfect to fuel “habituation eating”, and ultimately obesity.

Sugar is impregnated into cake carbohydrate or spread on the top as icing. Fat is used as a layer to make bland carbohydrates or even carbohydrates and protein more palatable, as in deep fried foods – where salt is added for good measure. Cheap beans are made more palatable for sale by adding the salt and sugar of ketchup.Salt is impregnated into carbohydrate ( chips and French fries).

Water, the foundation nutrient. Many children are metabolically confused because the water offered to them is laced with calories, primarily sugar and some metabolically noxious colourants. They then lose the distinction between thirst and hunger. When thirsty they might attempt to satisfy themselves by choOsing “food” rather than fluid (sugar laden drinks, iced cream ). The outcome is hypercaloric habituation.

It therefore might not be what you eat, but which combination one eats, that influences the health or disease of individuals. There is some evidence that individuals like to eat the same food and will repeat eating that ingestant by choice.

“Humans like variety, humans need variety, and humans need a balanced diet”. This may not have been the case with evolutionary man and it is certainly not the case with many animals. Those animals can adapt to a particular foodstuff (obviously one that is available) and then continue eating that foodstuff by choice, even where alternatives become available.

The legend has arisen that individuals need a “mixed and balanced” diet. As far as I am aware there is no evidence that this mixing needs to occur in the same meal. True enough, one needs the vitamins and one needs the different proteins, fat and carbohydrate. But does one need them simultaneously, wrapped around each other and made into tempting compotes?

Editorial comment: The science concurs:

The evidence for higher water intake, moderate protein and low sugar/salt no-smoking intake is self-evident except to sugar, beverage and cigarette manufacturers, marketeers and addicts. But the fraudulent promotion of the low saturated fat (ie meat), low-cholesterol , high carbs regime for all remains a big problem.

Dr Ancel Keys PhD (1904-2004) was a revered polymath traveler, oceanographer biologist turned physiologist nutritionalist (Biology of Starvation; the K Ration) , who correctly recognized and promoted the Mediterranean Diet (>35% fat), and long outlived his critics. But he and his followers set USA-led nutrition and health back 50 years with his wrongly interpreted Seven Countries study claiming that atheroma was caused by saturated fat- related hypercholesterolemia, thus promoting the Omega6PUFA low cholesterol diet and cholesterol-busting statins- but not explaining the question of fatal sudden death- coronary thrombosis posed by Sir George Pickering in 1964.

Keys may still be laughing his head off at the $billions he made for the Fast-Food industry & Big Pharma, and the millions of quality health years he cost gullible Americans and their ilk with his wrong high-omega6 diet and thence the money-spinning statins-for-all poison myth.

After the decades of derision poured as a result on the ketogenic high-fat-protein low sugars Atkins diet, the Disease-monger (Food, Sugar, Disease, Big Pharma) Industries will scoff, as they recently mocked sports physiologist Prof Tim Noakes’ conversion to high-fat ketogenic diet for those with the appropriate physiology, hisReal Meal Revolution . . Some cardiologists and dieticians even attacked him publicly for promoting scientific evidence against the high-carbs lowfat diet, including theWomens Health Initiative , not Big Pharma wishful thinking taught by the academics and clinicians whose livelihoods depend on their promoting Big Pharma and other new-tech products..

Read Noakes’ modern nutrition bible, the American science writer Gary Taubes’ The Diet Delusion(2009); and read the British Dr James le Fanu’s earlier Rise and Fall of Modern Medicine (1999 London pp 323-376), that dissected Keys’ toxic cholesterol-busting mythology, including statins that are now promoted for all seniors.

Its not a question of statin denialism since such drugs may have an appropriate place in severe hypercholesterolemia. Over all, the majority of hypercholesterolemic and CVD patients will do better on multisystem-beneficial metformin (antioxidant, antiinfective, antithrombotic, antidiabetic, insulin-sensitizing, appetite-reducing, weighloss-promoting), titrated to tolerance; with modest other essential multibeneficial supplements- (water; fish oil, coconut oil, DMSO, all vitamins especially BCo, C,D and K2; minerals especially magnesium, zinc, chromium, selenium and iodine; and other aging-and -diet-conditioned deficiencies of eg CoQ10, arginine, alphalipoic acid, carnitine, ribose, carnosine, acetylcystine, garlic, cinnamon, proline etc. ) than a multisystem-toxic statin.

THE SYDNEY HEART DIET STUDY And now the truth emerges yet again, that debunked Keys’ high Omega6 diet theory: as it did in the original ignored but landmark Sydney Heart Diet Study report in an elite 1978 journal (Adv Exp Med Biol.) aboutLinoleic Acid with Low fat, low cholesterol diet in secondary prevention of coronary heart disease. Woodhill JM, Leelarthaepin B, ea) discrediting Keys’ (and the USA Govt) postulate. The new 35year followup 2013 BMJ multicentre paper (Ramsden, Leelarthaepin Bea) from the Universities of Sydney, N Carolina and Illinois and the USA NIH : Use of dietary linoleic acid for secondary prevention of coronary heart disease and death: evaluation of recovered data from the Sydney Diet Heart Studyreevaluated effectiveness of replacing diet saturated fat (from animal fats, margarine, shortenings) with omega 6 linoleic acid Om6LA (safflower oil/margarine ) for a mean of 39months; in a single blind, parallel randomized controlled trial in 1966-73 in 458 men 30-59 years, with recent coronary event. Controls received no specific diet instructions. Non- dietary aspects equivalent in both groups. Results The intervention group (n=221) after only 3.25 years had 62-70% higher rates of death and CHD and CVD than controls (n=237; P=0.04-0.05)) (all cause 17.6% v 11.8%), Conclusions Advice to substitute PUFA for saturated fats is a key component of worldwide dietary guidelines for CHD risk reduction. However, clinical benefits of the most abundant PUFA Om6LA , have not been established. In this cohort, substituting dietary LA in place of saturated fats increased the rates of death from all causes, CHD and CVD. Updated meta-analysis of linoleic acid intervention trials showed no evidence of CVD benefit. These findings (could) have important implications for worldwide dietary advice to substitute Om3LA , or PUFA in general, for saturated fats.

THE MESA STUDY:The Sydney Diet Heart Study outcome has just been confirmed again by the Dec 2013 Harvard USA MESA study (de Olivera, Mozaffarian ea J Am Heart Assoc.) Circulating and Dietary Omega-3 and Omega–6 PUFA and Incidence of CVD in the Multi-Ethnic Study of Atherosclerosis. in 6 USA centres, which confirms that higher intake and levels of fish oil (but not ALA or Om6PUFA) halves CVD: Over 10 years, in a multiethnic cohort of 2837 US adults- mean age 61.4yrs at outset- plasma PUFAs measured at baseline (2000-2002), and dietary PUFAs , through 2010 during 19 778 person-years of follow-up, circulating n-3 eicosapentanoic acid EPA and docosahexanoic acid DHA inversely associated with incident CVD, with extreme-quartile hazard ratios (95% CIs) of 0.49 for EPA (0.30 to 0.79; Ptrend=0.01) and 0.39 for DHA (0.22 to 0.67; Ptrend<0.001). No significant associations with CVD were observed for circulating n-3 alpha-linolenic acid ALA or n-6 PUFA (linoleic acid, arachidonic acid). Associations with CVD of self-reported dietary PUFA were consistent with those of the PUFA biomarkers. Both dietary and circulating eicosapentaenoic acid and docosahexaenoic acid, were inversely associated with CVD incidence. These findings suggest that increased consumption of n-3 PUFA from seafood (but not alpha-linolenic acid or n-6 PUFA), may prevent CVD development in a multiethnic population.

But then we senior medics born around WW2 were schooled in the English /Scottish (not American) medical tradition of Drs Cleave, Burkitt, Painter & Campbell’s Saccharine Diseases, refined sugar, boozing, smoking and physical indolence-TV sloth as the chief causes of the burgeoning post-WW2 epidemic of obesity, diabetes, vascular disease, cancer and violence.

Humans rarely need what Big Pharma, science invents for megaprofits. We have known for 50 years that the current pandemic of degenerative and modern infectious diseases is due to bad diet – fast-food – and slothful lifestyle, tampering for megaprofit with food production and the environment, and reversible by correcting these factors with exercise, fresh whole food and organic farming, and avoidance of boozing, smoking, TV sloth, and continuous wars for profit, especially the Breast-and -Prostate Screening wars for the $billions to be made from screening aging men and women for early ie silent cancer.

The Sydney and MESA studies quoted thoroughly debunk the fast-food high Om6/carbs low fat diet promoted the past 50 years by the Food and Disease Industry, and by the Peskin-Rowen Om6 PEO and the statins-for-all hypotheses; and the nonsensical UK Wald and Law Polypill including high-risk statin-aspirin-betablocker -diuretic-ACEI for all senior citizens. . Even an advertorial Wikipedia entry promoting such nonsense has been allowed…

BALANCING INTAKE OF ANIMAL/DAIRY PROTEIN -SFA WITH MARINE Om3 PUFA, PLANT MCT & Om6, without added refined/concentrated sugars like fructose and cornstarch:As Mike Howard the Health Ranger writes this week, healthful pasture-fed butter is back, and margarine debunked even by its manufacturers; and almost half the USA states moving to enforce labeling of GMO foodstuffs so that consumers can choose what they buy. .

and biochemist GD Lawrence from Dept Biochemistry, Long Island University, NY writes in May 2013 Adv Nutr.Dietary fats and health: dietary recommendations in the context of scientific evidence: Early studies showed that saturated fat SFA diets with very low levels of PUFAs increase serum cholesterol, whereas other studies showed high serum cholesterol increased the risk of coronary artery disease (CAD). The evidence of dietary SFA increasing CAD or causing premature death was weak. Over the years, data revealed that dietary SFAs are not associated with CAD and other adverse health effects or at worst are weakly associated in some analyses when other contributing factors may be overlooked. Several recent analyses indicate that SFAs, particularly in dairy products and coconut oil, can improve health. The evidence of ω6 polyunsaturated fatty acids (PUFAs) promoting inflammation and augmenting many diseases continues to grow, whereas ω3 PUFAs seem to counter these adverse effects. The replacement of SFA in the diet with carbohydrates, especially sugars, has resulted in increased obesity and its associated health complications. Well-established mechanisms have been proposed for the adverse health effects of some alternative or replacement nutrients, such as simple carbohydrates and PUFAs. The focus on dietary manipulation of serum cholesterol may be moot in view of numerous other factors that increase the risk of heart disease. The adverse health effects that have been associated with SFA in the past are most likely due to factors other than SFAs. This review calls for a rational reevaluation of existing dietary recommendations that focus on minimizing dietary SFAs, for which mechanisms for adverse health effects are lacking.

TheUniversity Oregon Linus Pauling Micronutrient Centre website on EFAs has not apparently been updated with the latest MESA and Sydney trial reports; but it advocates (from Japan, and American Heart Association recommendations) Om3 fishoil intake of 2-4gm/day and Om6LA perhaps three times that- rather than the Keys-based 20:1 Om6:Om3 low SFA high carbs balance that has done so much harm in our lifetime.

BENEFITS OF FISH OIL AND COCONUT (MCT) OIL: are achieved by taking a tsp of clean (eg Baltic) codliver oil or a gm of fish oil concentrate a day; and no Om6LA supplement other than as a salad/pasta dressing; combined with liberal virgin coldpressed coconut oil for massage, cooking, and food dressing, or as a desertspoon+ a day..

TheWiki Health entryfor coconut oil usefully still notes the historical deliberate- profiteering- fallacious marketing bias against coconut oil- SFA- which has now been again debunked by the Sydney and MESA studies: Advocacy against coconut and palm oils in the 1970s and 1980s due to their perceived danger as a SFA saturated fat caused companies to substitute trans fats instead of them. Many health organizations (still) advise against the consumption of high amounts of coconut oil due to its high levels of SFA, including the USA FDA & ADA, the UK NHS, the WHO,[3] International College of Nutrition, and American Heart Association,[7]Coconut oil contains a large proportion of lauric acid—a SFA that raises blood cholesterol levels by increasing the amount of high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. Most of the increase is however HDL cholesterol, hence the ratio of total to HDL cholesterol is decreased.[30]A decreased ratio indicates reduced risk for heart disease.[31]It is also found in significant amounts in laurel oil, palm kernel oil (not to be confused with palm oil), and human and animal breast milk.This may create a more favourable blood cholesterol profile… Because much of the saturated fat of coconut oil is in the form of lauric acid, coconut oil may be a better alternative to partially hydrogenated vegetable oil when solid fats are required.[34] In addition, virgin coconut oil (VCO) is composed mainly of medium-chain triglycerides,[35]which may not carry the same risks as other saturated fats.[34][36

Similarly, the Wiki entry on Medium-chain triglycerides ie coconut oil- states its nutritional benefits without any harms: MCTs are considered good biologically inert source of energy that the humans find reasonably easy to metabolize. MCTs have potentially beneficial attributes in protein metabolism … and.. their tendency to induce ketogenesis. Due to their ability to be absorbed rapidly by the body, MCT have use in the treatment of malabsorption ailments. and neurodegenerative disorders (e.g. Alzheimer’s, Parkinson’s disease)[14] and epilepsy through the use of ketogenic dieting.[15][16] Serum high-density lipoproteinis increasingly elevated as the chain-length of triglyceride decreases.[17]

But current Cochrane review of controlled trial publications to 2013 confirms “Vaccination of pregnant women is recommended internationally, while healthy adults are targeted in North America. The overall efficacy of inactivated vaccines in preventing confirmed influenza has a NNV of 71 (95% CI 64 to 80). . Live aerosol vaccines have an overall effectiveness corresponding to a NNV 46 (95% CI 29 to 115). Vaccination had a modest effect on time off work and had no effect on hospital admissions or complication rates. Inactivated vaccines caused local harms. CONCLUSIONS: Influenza vaccines have a very modest effect in reducing influenza symptoms and working days lost in the general population, including pregnant women. This review includes 90 studies, 24 of which (26.7%) were funded totally or partially by industry. Out of the 48 RCTs, 17 were industry-funded (35.4%).

A current German review Methodological quality of systematic reviews on influenza vaccination. Fourty-six systematic reviews fulfilled the inclusion criteria. Average methodological quality was high but variability was large (AMSTAR range: 0-11). Quality did not differ significantly according to vaccination target group. Cochrane reviews had higher methodological quality than non-Cochrane reviews (p=0.001). this was due to better study selection and data extraction, inclusion of unpublished studies, and better reporting of study characteristics (all p<0.05).

20/1/2014 Protecting us from the new year northern hemisphere viruses: natural antibiotics- Vitamins C & D: avoiding vitamin denialism as cause of more deaths.

Abstract: The Semmelweis Reflex is about rejecting, deriding important new scientific discoveries or any serious sincere statement/action. I didnt fully appreciate the importance of that age-old human (mostly male) evil – mocking, martyrdom and murder by denialism- until I started this review of the current flu season threat and the role of supplements, and researched pioneer medical martyrs Drs Ignaz Semmelweis, Jack Drummond and Linus Pauling as paradigms of the scourge of modern vested-interest denialism and falsehoods, in medicine as much as politics, religion etc..

In fact, just as it is negligence to deny (as Semmelweis’s persecutors did) gloving up or properly washing hands between examining patients , or ensure that every adult has bloodpressure checked occasionally, it is clearly bad practice not to ensure that everyone – especially the young and old, takes a multinutrient plus extra vigorous dose vitamins D3 and C, plus some protective herbs- garlic, cinnamon, ginger, origanum; and fish oil and/or coconut oil if not both; and drastically cut down sweetness intake- especially fructose, sucrose and aspartame that now pervade all mass- produced food and drinks..

update 21 January 2014: URGENT: THE 2014 FLU EPIDEMIC: “High H1N1 prevalence and mortality rates a concern: Type A (H1N1) influenza, the commonest flu virus in Canada this year, has a higher than anticipated mortality rate causing some to wonder if it’s virulence has increased. The worrisome factor “is the reported mortality rate,” says McGill University. As of Jan. 13, there were twenty confirmed deaths in Canada attributed to H1N1. “There are more deaths than what we expect for the regular H1N1 influenza, The strain this year could be more virulent . 96% of this year’s lab -confirmed influenza is H1N1. The virus is unusual in that it appears to affect younger people more than other strains of seasonal influenza. People 20 to 65 are being hit harder than usual, comprising 52% of flu cases. However, if you look at Europe, it’s still H3N2. Its an example of how you never know what the flu is going to do.” Alberta confirmed a death on Jan. 8, due to the virus H5N1, an avian virus. The deceased woman had recently returned from China. The mortality rate is higher with H5N1 than H1N1, “but fortunately, it’s not an easy virus to transmit”. So far, it seems that there are no cases of H5N1 transmission from human-to-human. It seems like the cases of H5N1 are few and far between and related to contact with birds in China. Patrick Janukavicius, Montréal, Quebec. In the same period, at least 20 children have reportedly died of the same strain in USA.

1 Jan 2014 CURRENT INFLUENZA STATUS: The 22 December solstice is the sun at its southern nadir seen from planet Earth, the onset respectively of real winter in the Northern hemisphere, and real summer in South Africa. Last year the Gregorian New Year heralded a fierce flu season in the northern hemisphere, and as usual feathered- and jet-propelled air travel brought the corresponding surge at the bottom of Africa.

And ominously, the Plagues & Pandemics (Howard Phillips 2012) of temperate climates that did so much historically to mould global demography not least the past 360 years in South Africa ( –STDS- pox, bubonic, polio, cholera, influenza, and now tuberculosis, Mad Cow disease, and HIV-AIDS). and especially antibiotic-resistant germs – are all on the increase despite (or because of) the increasingly futile $trillion armamentarium of 20th century designer vaccines and other antimicrobials..

Pneumonia is a welcome friend of the old, often rapidly relieving prolonged degenerative incapacity; such ending mostly by virus respiratory infection the gateway for the final bacterial infection.

Unlike the selflimited coronavirus common cold, breath-and hand-borne type A influenza, although usually mild in the well, is the commonest trigger in the frail. Many of us in our (grand)parents’ time lost relatives in the 1918/1919 “Spanish” H1N1 flu pandemic. But that was a unique global catastrophe because it killed mostly armies of healthy men, and then young working adults, apparently from cytokine storm, with 30 % of the workforce out for up to3 weeks if not 20% mortality. This is harrowingly described in the recently published Letters ( to his Mother) of Dr Arthur Conan Doyle, who lost – apart from his first wife to TB- more young relatives to the flu than to warfare.

The recent spring months here – apart from seasonal allergies -have seen declining viral respiratory illness in Cape Town, with the upper respiratory accent often shifted down to more gastritis-enteritis .

But New Year 2014 UK and northern North America forecast and are having a wet if not white New Year. ‘Flu rates are reported already high and rising in USA and Canada– mostly influenza A H1N1(swine-avian flu-the main 1918/19 killer); including already 6 deaths in USA and 3 in Canada.

but not in Europe, where the influenza (A > B) prevalence is still low and slightly more H3N2 than H1N1; in UK there has rather been been increase in RSV respiratory syncytial virus bronchitis in infants. . .

In fact by 28 December the exploding H1N1 deathtoll had hit 13 in Texas alone; especially in youths; with increasing Tamiflu resistance reported eg in Missisippi.. On 24 Dec the USA CDC mailed an emergency Advisory Notice to Clinicians: Early Reports of pH1N1-Associated Illnesses for the 2013-14 Influenza Season: From November through December 2013, CDC has received a number of reports of severe respiratory illness among young and middle-aged adults, many of whom were infected with influenza A pH1N1 pdm09 virus. Multiple pH1N1-associated hospitalizations, including many requiring intensive care unit (ICU) admission, and some fatalities have been reported. While it is not possible to predict which influenza viruses will predominate during the entire 2013-14 influenza season, pH1N1 has been the predominant circulating virus so far. For the 2013-14 season, if pH1N1 virus continues to circulate widely, illness that disproportionately affects young and middle-aged adults may occur.

Our regional South African Communicable Diseases Institute says , “H1N1 was documented here from April to September. But of 2566 pts with severe respiratory illness for January to October 2013 enrolled and tested at the five sentinel sites, only 6% were positive for influenza – mostly virus -H1N1. A pneumonia case in Cape Town was found to be due to Leigionnaire’s.

Now from China 147 human cases of avian influenza H7N9 have been confirmed including 48 deaths. – especially from poultry contact. No vaccine is currently available for avian influenza (H7N9) virus.

SAPA–AFP, 10 December 2013: Resistant flu virus keeps contagiousness. A mutant form of the H7N9 flu virus that is resistant to frontline drugs is just as contagious as its non-resistant counterpart, according to a study, published inthe journal Nature Communications. The virus has claimed dozens of lives since its outbreak in February. H7N9 is believed to have spread to humans from poultry, where it circulates naturally. The World Health Organisation (WHO) said on its website that “so far”, no evidence has emerged of “sustained” transmission of H7N9 among people.

So never mind the common cold coronaviruses and many other prevalent infections, increased caution is due against all common diseases at this season- both the USA H1N1 swine flu circulating the past few years, and now the Chinese H7N9 flu. . And the MERS-Co Virus Middle-East SARS-type outbreak has not gone away… 9 new cases reported the past week or two from the KSA alone .–the-deadly-middle-east-coronavirus-outbreak/

A current NEJM has a new report of a trial of quadrivalent Vaccine for Prevention of Mild and Moderate-to-Severe Influenza in Children by vaccine manufacturers GSK. The vaccine reduced severity by perhaps 70%- but at a cost of 1.5% serious adverse events, 50% more than the control group (hepatitis A vaccine only). The question remains- why risk flu vaccine’s ~1.5% serious adverse events when a single high dose of vitamin D3 300 000iu even just annually, and regular vitamin C with a multivite including zinc and selenium (at trivial cost ) largely cover one against a multitude of infections including AIDS and TB, and all degenerative health problems?

PRECAUTIONS:

Is it coincidence, or divine evolution, that we have had available at low cost for about 60 year (never mind zinc, selenium, iron, iodine, vitamins A and vitamin E) two safe natural major antimicrobials in vigorous safe dose – vitamins C and D3? Medico-Pharma Big Business and governments have been heavily discrediting and ruthlessly suppressing these for their own profiteering vested interest even as plagues of HIV, TB, influenza rage, and Big Business determinedly profits hugely from killer smoking and alcohol sales despite increasing marketing restriction? South Africa- a major producer of alcohol and tobacco-smoke, and fossil-fuel-burning power stations, factories and motorvehicles – continues to lead the world with the highest road and respiratory death rates despite zealous attempts to reduce their lethal use.

Apart from optimal hygiene including avoiding livestock and poultry contact, smoking, alcoholism and pollution including swimming and sick buildings- air-conditioning- what can we take to minimize avoidable influenza ie immune depletion risk? apart from enough sunshine, exercise, rest, sleep, walking barefoot, not carrying a cellphone, and good mixed fresh organic diet? The clinical benefit of influenza vaccines is anything but proven, and the adverse risks appreciable.

The ATBC vits A+E trial (isolated highdose vits A and E) was one such farce in very high risk smokers in an icy climate. . Others have been the recent Norwegian trial using only up to 1000iu vit D supplement a day,

*a commercial multisupplement in the TACT post-heart attack trial – but the composition of the multisupplement included only deficiency-disease prevention microdoses of micronutrients including 100iu vitamin D3/d and equally negligible vitamin K- not pharmacological doses of key vitamins eg vits B, C, D & K2 that are well proven to greatly reduce infections and chronic degenerative diseases ;

* the Physicians’ Health Study randomized elderly professional men to placebo or combinations of vitamin C (500 mg synthetic ascorbic acid), vitamin E (400 IU of synthetic alpha-tocopherol), beta-carotene (50 mg Lurotin), and a multivitamin (Centrum Silver – this included anti-deficiency disease low dose of all common vits and minerals BUT only 400iu Vit D3), .

* The third study- on lowdose (traditional anti-deficiency disease) Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer was simply a literature review of 26 best-quality published trials of microdoses – not pharmacological safe macrodoses.

ie these three trials published in this Annals Internal Medicine issue to please Big Pharma advertisors to discredit supplements shared the usual problem of now well-known futile lowdose supplement doses at least of vitamins D3 and K, if not also vitamin C in the multigram dose scientifically promoted by the Drs Stone- Klenner-Pauling followers.

Sir Jack Cecil Drummond (1891-1952) was one of the world’s pioneer 20th century biochemists and nutritionists in UK, from 1916- 1952 discovering or defining and promoting under his world-famous biochemist professors Rosenheim, Halliburton and Funk the role especially of vits A, B, C and E. Thanks to his and Churchill’s forceful vision and foresight, he oversaw food supply and diet and thus keeping Britons healthy through and after WW2. He was so successful in promoting healthy cheap and unpatentable micronutrients and natural fresh food (in the face of the mushrooming megaprofit processed food and designer drug industry) that it speculatively led to his and his family’s 1952 assassination by competing interests in France –The Vitamin Murders, Fergusson 2007. .

MURDER BY DENIALISM: It is incontrovertible common cause that irrational and often jealous medical denialism costs endless lives:
* Scurvy prevention:Dr James Lind (who did the first ever recorded clinical trial) showed by 1750 that sailors’ scurvy on long sea voyages was preventable; but despite his pioneer discovery, the British navy cost the lives of thousands more seamen from scurvy when the Admirals neglected for 50years until the Napoleonic Wars to supply the fresh produce- eg limes – that rapidly cured and prevented the lethal scourge.

This despite the fact that another UK navy surgeon Dr John Woodall had already over 130 years earlier- by 1617 – published in UK The Surgeon’s Mate stating We have in our owne country here many excellent remedies generally knowne,- Scurvy-grasse, Horse-Reddish roots, Nasturtia Aquatica, Wormwood, Sorrell, and many other good meanes… to the cure of those at home…and Sea-men returned from farre who by the only natural disposition of the fresh aire and amendment of diet, nature herselfe in effect doth the Cure (of scurvy- for which antiscorbutic citrus had been known since antiquity) without other helps. the Lemmons, Limes, Tamarinds, Oranges, and other choice of good helps in the Indies… do farre exceed any that can be carried tither from England.

* Childbed fever prevention: in 1865 Dr Ignaz Semmelweis (1818 -’65) an AustroHungarian Roman Catholic ob-gyne in Vienna, was locked up, and beaten to death within weeks, because he showed – to the outrage of his peers- that handwashing with chlorinated lime eradicated the epidmic puerperal fever (three times that in the midwives’ ward) in the doctors’ labour wards; 70years before Thir Reich terrorists took charge, his senior colleagues reacted violently to his progressive promotion of (what was already more advanced British and French) hygiene and science, and his urging them to wash their hands after examining corpses before examining women in labour.. . Tragically for Semmelweis and new mothers in the Hapsburg empire then, Pasteur (b 1822) and Lister (b 1827) ‘s germ antiseptic discoveries were already being implemented further west, but had not yet been publicized.

*metformin after centuries of use as an antidiabetic herb galega officinalis, and its extraction as an antidiabetic in 1922, came into increasing use globally from the 1950s as the best treatment for type 2 diabetes, but the USA- to protect their own new patent antidiabetic drugs – ruthlessly suppressed its use there (like that of the natural salt lithium for manic depression) for 40years till the mid-1990s.

*AIDS and ART denialism: until 5 years ago in South Africa the overwhelming-majority “people’s” government (with the country’s vast resources), and its successive “health” ministers, cost the lives of an estimated 300 000 AIDS victims through sufferers – indigent state dependents- being denied antiretroviral ART drugs, (never mind still till now denied quality education and civil security, and thus adequate basic nutrition, and meaningful housing, jobs and thus hope.) Genocidal AIDS denialism about which the still-ruling (since 1994) leadership cadre did nothing until under intense international pressure and repeated Constitutional Court orders, combined with political rival factioneering in the ruling party, they ousted the denialist president and his denialist Disease Minister in 2008.

DENIALISM TARGETS IN NUTRITION:

VIGOROUS VITAMIN C ASCORBIC ACID PHARMACOTHERAPY : Much effort and Big Pharma money has been spent to denigrate the irrefutable science-based work (between their advocacy years shown) of Drs Irvine Stone (1934-1984), Fred Klenner(1948-74) and Linus Pauling (1970-1991) of antibiotic dose >50 to 1000 mg/kg/d pure vitamin C (not the antiscurvy 10mg/d) – as a universally needed essential in primates. We primats, like guineapigs and a few birds and fish species, are among the few that do not make their own since we lost the needed gene and thus enzyme in our evolution..

It took about 150 years after Lind’s publication for the antiscorbutic factor to be named as vitamin C by Dr Jack Drummond, another 10 years for it to be assayed and its structure proven- but despite the pioneering clinical work of Dr Fred Klenner in the 1950s proving the lifesaving benefit of tens of grams a day intravenously, it took another 20 years before Dr Linus Pauling took up Dr Irvine Stone’s conviction and put highdose vitamin C on the world Nobel prize map; just on Pubmed, vitamin C has >51 000 citations since 1921, and intravenously in 763 entries since 1946, with Dr Fred Klenner reporting it intravenously asmajor antibiotic in the Southern Medical journal from 1948..

The 2009 book Injectable Vitamin C and the Treatment of Viral and Other Diseases collection of medical journal papers from the 1930s to 2006 details the exhaustive scientific evidence proving the uniform benefit of even 1gm a day vit C both as an antimicrobial antiinflammatory antioxidant and immunomodulator against major crippling / lethal diseases from polio to tuberculosis, pneumonia, hepatitis, rabies, encephalitis, neuritis, poisoning, cancer, and pancreatitis;

and the persistent resistance of the FDA and other multinational Regulators to recognize (so as to protect their domestic patent drug manufacturers- Big Pharma and their politician and civil service lobbyists )- such uniquely safe and effective natural drug therapy. The final chapters of that 2009 book pose the crucial questions of overwhelming vested interest by the organized medical – hospital –pharmaceutical mega-industry and governments in not eradicating preventable disease, the Big Pharma banning of natural effective remedies- The Origin of the 42-Year Stonewall of Vitamin C, and Medical Resistance to Innovation,

The University of Oregon, the Riordan-Gonzalez group and more recently Hemila and Chaker‘ and Ullah et al’ s 2012 reviews have published much validating what Drs Goodall, Lind, Drummond, Stone, Klenner, Paulingand Cameron started.

paralled by Prof Robert Heaney (MD 1951) at Creighton University, osteoporosis and nutrition authority with 119 vitamin D papers on Pubmed since 1982, over 400 publications to date;

succeeded by Prof Mike Holick(PhD 1971, MD 1976) with 391 publications on vitamin D since 1970 on Pubmed, who has done more than most to show that the maximum daily body production of vitamin D3 with plenty of sunlight is enough to prevent rickets and reduce all disease, but nowhere near the pharmacologically therapeutic 80iu/kg/d needed to maintain a vigorous all-disease protective bloodlevel of 60-100ng/ml.

and Dr John Cannell (MD 1976, registered psychiatrist from 1993, nutritionalist), a legendary whistleblower . who successively campaigned against #cigarette smoking; and uncovered: # the cigarette-smoking (Black Lung) compensationitis fraud of miners’ pneumoconiosis; #the fictitious inflated “above national average” school results (Lake Woebegone) that all states were inventing and reporting (as is still happening – mass government deception- in South Africa) ; then the # recovered memory therapy (RMT) scandal – a form of psychotherapy in which patients recovered memories of abuse that they had no previous memory of. Such therapy resulted in false memory syndrome (FMS) of events that never occurred as well as an epidemic of multiple personality disorder (MPD), a rare disorder historically conceived of as being a hysterical disorder. Unfortunately, many MPD patients believed the psychiatrist conducting the RMT and went home to falsely accuse their parents and others of horrendous acts that never occurred. Cannell teamed up with two Harvard professors to write a peer reviewed paper on RMT, debunking the witch-hunt; then since the 1990s researching and promoting # vitamin D deficiency as major cause of much psychopathology including autism, and vigorous vitamin D therapy to correct multiple diseases, through the Vitamin D Council. He has (co)authored some 13 papers, and published a book. .

Now a major longterm German Cancer Research screening programhas just publishd the 2002-2013 ESTHER study (Perna ea) of 10 000 citizens followed with serial 25OH vit D levels; to assess the association of apparently unsupplemented vit D levels with fatal and nonfatal CVD in the same study population. Follow-up data, including survival status, up to over 9 years. Comparing subjects with 25(OH)D levels below 12ng/ml and above 20ng/ml resulted in the lower vitamin D level cohort showing a higher hazard ratio of 1.27 (95% confidence interval = 1.05-1.54) for total CVD and 1.62 (1.07-2.48) for fatal CVD in a model adjusted for important potential confounders. No significant association for nonfatal CVD was observed. In dose-response analysis, we observed an increased cardiovascular risk at 25(OH)D levels below 30ng/ml. Results for CHD and stroke were comparable to the results obtained for the composite outcome CVD. Our results support evidence that low 25(OH)D levels are associated with moderately increased risk of CVD, BUT the observed association is much stronger for fatal than for nonfatal events.

But the benefit of sunlight in healing tuberculosis has been used for well over a century; while the Google antibiotic benefit of calciferol on Pubmed goes back at least to 1950.

Since the toxic dose of vitamin D long term reportedly may be as high as 600 000iu/day or a blood level well >150ng/l , imagine how much better the antimicrobial benefit of vitamin D3 at 80 to 100iu/kg/day or pro rata – even higher eg 10 000+iu/day for obese people who sequester more vit D in fat. .

Dr Robert F Cathcart wrote 30 to 20 years ago in Med Hypotheses. 1981 Vitamin C, titrating to bowel tolerance, anascorbemia, and acute induced scurvyThe amount of oral ascorbic acid tolerated by a patient without producing diarrhea increase somewhat proportionately to the stress or toxicity of his disease. Bowel tolerance doses of ascorbic acid ameliorate the acute symptoms of many diseases. Lesser doses often have little effect on acute symptoms but assist the body in handling the stress of disease and may reduce the morbidity of the disease. However, if doses of ascorbate are not provided to satisfy this potential draw on the nutrient, first local tissues involved in the disease, then the blood, and then the body in general becomes deplete of ascorbate (Anascorbinemia and Acute Induced Scurvy). The patient is thereby put at risk for complications of metabolic processes known to be dependent upon ascorbate. 1984 Vitamin C in the treatment of acquired immune deficiency syndrome (AIDS). evidence is that massive doses of ascorbate (50-200 grams per 24 hours) suppress the symptoms of the disease and can markedly reduce secondary infections. In combination with usual treatments for the secondary infections, large doses of ascorbate will often produce a clinical remission which shows every evidence of being prolonged if treatment is continued. .. despite continuing laboratory evidence of helper T-cell suppression. There may be a complete or partial destruction of the helper T-cells during an initial infection that does not necessitate a continuing toxicity from some source to maintain a permanent or prolonged helper T-cell suppression. However, it is possible ascorbate may prevent that destruction if used adequately during that prodrome period. Emphasis is put on the recognition and treatment of the frequent intestinal parasites. Food and chemical sensitivities occur frequently in the AID syndrome and may aggravate symptoms considered to be part of the AID syndrome. A topical C-paste has been found very effective in the treatment of herpes simplex and, to a lesser extent, in the treatment of some Kaposi’s lesions. Increasingly, clinical research on other methods of treating AIDS is being “contaminated” by patients taking ascorbate. 1991A unique function for Vitamin C is as reducing substance, electron donor. When vitamin C donates its two high-energy electrons to scavenge free radicals, much of the resulting dehydroascorbate is re-reduced to vitamin C and therefore used repeatedly. Conventional wisdom is correct in that only small amounts of vitamin C are necessary for this function because of its repeated use. The point missed is that the limiting part in nonenzymatic free radical scavenging is the rate at which extra high-energy electrons are provided through NADH to re-reduce the vitamin C and other free radical scavengers. When ill, free radicals are formed at a rate faster than the high-energy electrons are made available. Doses of vitamin C as large as 1-10 g per 24 h do only limited good. However, when ascorbate is used in massive amounts, such as 30-200+ g per 24 h, these amounts directly provide the electrons necessary to quench the free radicals of almost any inflammation, and reduces NAD(P)H and therefore provide the high-energy electrons necessary to reduce the molecular oxygen used in the respiratory burst of phagocytes. In these functions, the ascorbate part is mostly wasted but the necessary high-energy electrons are provided in large amounts.

A recent review from Atlanta Kearns eafound 30 papers which aggregate to show that annual vitamin D3 dose (not D2) of optimally 300 000 to 500 000iu (wholesale cost ~R5 in South Africa) for deficient adults is best for avoiding poor patient compliance with minimal risk and major benefit.

THE INFERIORITY OF VITAMIN D2 SUPPLEMENT: It should be noted that the long-used Lennon’s Strong Calciferol datasheet (1974 updated 2004) does not indicate that this 50 000iu tablet labelled ‘calciferol’ is in fact vitamin D2 (ergocalciferol), not the fourfold more potent cholecalciferol D3 formed by sunlight in the skin. This is disclosed only on the Lennons website.. and in the South African Medicines Formulary. So ‘Strong Calciferol’ in South Africa (actually the D2 not D3 form of calciferol) is convenient but seriously deceptive mislabeling- much weaker than the ideal vitamin D3, and therefore its effect unpredictable compared to D3- in fact Dierkes ea Norway show that giving D2 may actually lower 25OH vit D level in the blood.. Sadly, despite this being reported to the local manufacturers and authorities, no correction of the clinically serious misperception created by the Strong Calciferol label and insert has been issued to health practitioners by the Medicines Control Council and the manufacturer Aspen-Lennons.

A recent 8yr study in Cape Town blacks Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in South AfricaMartineau, Nhamoyebonde ,Wilkinson ea confirmed that vitamin D deficiency (serum 25(OH)D <20 mg/L) is associated with susceptibility to tuberculosis (TB) in HIV-uninfected people in Cape Town as it is Europe. Vitamin D deficiency was present in 62.7% of 370 participants and was associated (OR ~5.4) with active TB in both HIV-uninfected and HIV-infected -(P < 0.001) people. Vitamin D status varied according to season: 25(OH)D concentration was double in summer-January- March compared to winter (23 vs 12ng/l; P < 0.001). Reciprocal seasonal variation in TB notifications was observed:lowest in autumn and highest in spring October through December (4,2 vs. 5; P < 0.001). Vitamin D deficiency is highly prevalent among black Africans in Cape Town and is associated with susceptibility to active TB both in the presence and absence of HIV infection.

and finally, a month ago JAMA published from Marianna Baum, Richard Marlink ea the universities of Miami, Harvard and Florida Effect of Micronutrient Supplementation on Disease Progression in Asymptomatic Antiretroviral-Naive HIV-Infected Adults in Botswana A Randomized Clinical Trial, that Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive. 2 year supplementation with either daily vitamins BCo, C and E, selenium alone, or B,C,E with selenium vs placebo: study conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART between 2005 and July 2009. Results participants receiving the combined supplement of vitamins plus selenium vs placebo had half the risk of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46); and secondary events of combined outcomes for disease progression or AIDS-related death, whichever occurred earlier [adjusted HR, 0.56); . There was no effect of supplementation on HIV viral load. Multivitamins alone and selenium supplementation alone were not statistically different from placebo for any end point. Reported adverse events were adjudicated unlikely related to the intervention, and there were no notable differences in incidence of HIV-related and health-related events among study groups.Conclusions and Relevance In ART-naive HIV-infected adults, 24-month supplementation with a single supplement containing vitamins BCo,C,E and selenium was safe and significantly reduced the risk of immune decline and morbidity. Micronutrient supplementation may be effective when started in the early stages of HIV disease.

THE PARADOX OF THE GLUCOSE- ASCORBIC ACID- CHOLESTEROL- STEROID CASCADE: Is it coincidence, or evolution, that the basic animal fast-energy circulating anabolic substrates are glucose, fatty acids and aminoacids? from which basic glucose C6H12O6 ( from ingested fructose C6H12O6 and sucrose C12H22O11, or fats or protein) the liver manufactures the basic cardinal steroid cholesterol C27H46O. Then from cholesterol we metabolize by adding or splitting off carbon molecules the crucial anabolic and regulating human hormones- 1. ouabain C29H44O12 the adrenal hormone made also in the hypothalamus and heart ; adrenal), 2. active calciferol C27H44O the strengthening and reproductive secosteroid; 3 the prime sex/ reproductive steroids pregnenolone C21H32o2, and thence progesterone C21H30O2, testosterone C19H28O2, DHEA C19H24O2. and thence estradiol C18H24O2. and 4 the prime adrenal mineralo/glucocorticoid steroids cortisol C21H30O5, aldosterone C21H28O5.

But we primates and a few other species lost the ability to synthetise on demand in quantities of grams a day the crucial vitamin C ascorbic acid C6H8O6 that is key to all the above. And vested interests in the Disease Industry want us to believe the biological nonsense heresy that we must ingest minimal unprocessed foods- cholesterol, fats (especially dairy, marine oil Omega3 and medium-chain triglyceride- coconut oil) and abundant vitamins C and D3, but eat abundant processed foods- refined plant Omega6, refined carbs- fructose, sucrose, fruit juice, cooldrinks, cereals, confections- which overload causes insulin resistance and thus lipidemia, obesity- metabolic syndrome -diabetes, cancer and cardiovascular disease.

The Semmelweis reflex: A current Wiki essay sums up the current genocidal problems of deliberate deceptions/denialism in Diet, Vitamins and causality – for ruthless profit and possibly cynical eugenics: “The Semmelweis effect is a metaphor for the reflex-like tendency to reject new evidence or new knowledge because it contradicts established norms, beliefs or paradigms.The term originated from the saga of Dr Ignaz Semmelweis, who discovered that childbed fever mortality rates reduced ten-fold when doctors washed their hands with a chlorine solution before examining patients. His hand-washing suggestions were rejected by his contemporaries, often for non-medical reasons. For instance, some doctors refused to believe that a gentleman’s hands could transmit disease (see Contemporary reaction to Ignaz Semmelweis). In his book The Game of Life, Timothy Leary provided the following polemical definition of the Semmelweis reflex: “Mob behavior found among primates and larval hominids on undeveloped planets, in which a discovery of important scientific fact is punished”. The expression has found way into philosophy and religious studies as “unmitigated Humean skepticism concerning causality“.[2]”

Idealism, ethics may evolve; but the problem of human bigotry, self-interest and subjective ie personal bias do not diminish, they spread. It is classic that Semmelweis (1818-1865) the observant innovative Catholic medical scientist of his time (before microbes and antiseptics were known) was fatuously condemned not just by his jealous competing Vienna colleagues, but even by his progressive and reformist Copenhagen contemporary obgyn Prof Carl Levy (1808-1865)- who outlived him by only 4 months;

ironically at the same time that their Copenhagen contemporary Dr Soren Kierkegaard(1813-1855) was increasingly isolating himself on the lonely ethical journey against the convenience lazzez- faire tide, writing for ethical life and religion against the hypocrisy of the Church and becoming the father of both reformist theology and psychology. But unlike Semmelweis who was way ahead of the bioscience and humanity of his time, Kierkegaard stuck to and isolated himself in promoting the incompatible ie blind-faith-based religion – the dilemma of Abraham’s conviction (or delusion) to sacrifice his son- and ethical morality;

and closely followed by Rudolph Steiner (1861-1925) another more profound European thinker who bridged science, spirituality, progressive education, architecture, agriculture, natural medicine, nutrition, and social reform;

contrary to the rationalists of the 19th Century “Age of Enlightenment” and since, like British historian-philosopher -ethicist Winwood Reade(1838 – 1875) who published the enduring secularist’s bible The Martyrdom of Man (1872), of which Churchill wrote 25 years later “he was right but wrong to say it” on the book’s critique of the wrongs of war and religion, of mankind’s selfishness, corruption and destructiveness (by the greedy aggressive acquisitive minority) against the weak masses and the environment) that carries on worse in the 21st century than even the 20th century; and 150 years later bioscientist and philosopher Stephen Jay Gould (1941-2002) rationalized sadly the non-overlapping Magisteria of Science and Faith, objective “provable” science – which in fact is seldom immutably constant as is mathematics- and purely faith-based “unprovable” religious belief.

It was only a year ago that Richard Conniff published his column on Strange Behaviours, The Medical Martyrs. And the medical hero martyrs in this review- Semmelweis, Margaret Sanger, Drummond and Pauling – never made it onto his list.

But then nor did the modern medical freedom fighters Steve Biko, Agostinho Neto, Che Guevera. Jonas Savimbi, Neil Aggett, and the living spouse of Steve Biko, Dr Mamphele Ramphele….

Unlike eg Socrates, Hippocrates and Jesus of Nazareth, one of the five greatest polymath medical and ethical sages of all time Rabbi Dr Moses Maimonides (RamBam) avoided martyrdom by burying himself in practicing selfless medical service for sultan and peasants alike, and jurisprudence for his GreekoRoman based Islamic-Sephardic times and philosophy, like his guru predecessor Avicenna and his contemporary savant Averroes. .

– especially when patients are poor and thus malnourished, and plagued by diarrhoea and stress, TB, lipidemic vascular disease and cancer; and when antiretroviral ART- although life-saving- is even more diabetogenic and neurotoxic than untreated AIDs.

below are some of the most recent 94 studies of vitamin D and human infectionin published just in 2013:

New insights on the role of vitamin D in the progression of renal damage: Kidney Blood Press Res. 2013;37:667-78. . Lucisano S, Santoro D.ea Many studies indicate relationship between hypovitaminosis D and survival, vascular calcification, bone mineral metabolism, immune, cardiovascular and endocrine. Vitamin D analogs reduces proteinuria, in particular through suppression of the renin-angiotensin-aldosterone system (RAAS) and exerts anti-inflammatory and immunomodulatory effects. In particular vitamin D deficiency contribute to an inappropriately activated RAAS, as a mechanism for progression of chronic kidney disease (CKD) and/or cardiovascular disease. Human and experimental models of CKD showed that vitamin D may interact with B and T lymphocytes and influence the phenotype and function of the antigen presenting cells and dendritic cells, promoting properties that favor the induction of tolerogenic T regulators rather than T effectory. Interstitial fibrosis may be prevented through vitamin D supplementation. .

1/1/2014 again, its comforting that no new evidence of hepatotoxicity of genuine black ohosh; or kava; or (USA-grade) Herbalife products have been reported the past two years.

Teschke ea from Germany make the important point that herbaltoxicity is likely due to the “kava paradox”, that no toxicity is reported with ancient time-tested herbal remedies used appropriately by tradition in their fresh natural state and their countries of origin eg Pacifi islands; ,

but that adverse events occur with commerial eg alcohol-extracted and often preserved and old preparations, and in untested combinations with other substances especially statins, ethanol, and unknown viruses. .

The Herbalife company has just had to publish again an update rebuttalof bad papers wrongly implicating and accusing Herbalife. Their summary says:

World J Hepatol. 2013 Oct 27;5(10):601-2.. A correction of misinformation regardingHerbalife. Appelhans K, Najeeullah R, Frankos V. Herbalife International of America Inc, Torrance, CA The authors of the subject article by Senadhi et al from Indiana State University have misrepresented the safety and regulatory status of Herbalife‘s products. While we are very concerned with the unwarranted and unfavorable publicity that the inaccuracies listed could generate for Herbalife, we would welcome any inquiries that these authors may have to better clarify our commitment to the safety and quality of our products as has been demonstrated in part by our ability to establish positive relationships with regulatory authorities worldwide through continued cooperation and compliance. This letter clarifies the misinformation presented about Herbalife in the subject article

16 March 2012 it is comforting to note that there have been no new reports the past year of toxicity from these products.

In fact some lab work seems to favour black cohosh for cancer prevention;

while Herbalife has published objective rebuttals of toxicity from Herbalife other than in isolated countries where irregular ingredients were used in local manufacture:

World J Hepatol. 2011 Oct 27;3(10):275-7. Revisiting acute liver injury associated with herbalife products.Appelhans K, Smith C, Bejar E, Henig YS Herbalife International of America Inc., Torrance, CA 90502, United States. In the November 27, 2010 issue of the World Journal of Hepatology (WJH), three case reports were published which involved patients who had consumed various dietary supplements and conventional foods generally marketed as weight loss products. The reference to Herbalife products as contaminated and generally comparable to all dietary supplements or weight loss products is not scientifically supported. The authors provided an insufficient amount of information regarding patient histories, concomitant medications and other compounds, dechallenge results, and product specifications and usage. This information is necessary to fully assess the association of Herbalife products in the WJH case reports. Therefore, the article does not objectively support a causal relationship between the reported cases of liver injury and Herbalife products or ingredients.

As this colunm has previously reviewd about BC, women have died from or needed liver transplants after taking it.. Hence most Authorities have Black Box warning requirements Recurrences of liver reaction have been reported on rechallenge. These scattered cases can be argued away on metanalysis, but they cannot be ignored. One death or acute liver failure is unacceptable when BC is never an essential drug without other safe options.

Another study also published now (Wang ea from the FDA Centre for Drug Evaluation ) http://www.ncbi.nlm.nih.gov/pubmed/20920542 contradicts the German metanalysis with more basic toxicological data: “Computational analysis of positively predicted constituents showed … specifically, protocatechuic acid from black cohosh… predicted positive for liver toxicity endpoints also confirmed with literature findings”

Black cohosh is not physiological hormone replacement, BC is recommended by its proponents solely for menopause symptoms (it has no other benefits) for up to 6 months.

So why risk, use black cohosh at all?

Appropriate balanced hormone replacement – preferably human hormones, not xenohormones ie hormones not found in the healthy women, and not by swallowing it- is indicated permanently in all women .

As previouslly pointed out in this column, the International Menopause Society has summed it up in putting approriate HRT as the main agent(s) for menopause symptoms as well as for its permanent multisuystem benefits; and the human hormone gamma-aminobutyric acid GABA as the only alternative that is both safe and cleearly proven better than placebo for improving both hot flashes and sleep, anxiety. Used appropriately and with sensible monitoring and dose titration, all such hormone balance has no longterm risks.

MDICOLEGAL LIABILITY: under the new Conumae Protection Act CPA in South Africa, the pendulum has gone ridiculously too far. irrespective of the onus on manufacturers and promoters of any product, the onus is on the end-prescriber, end-dispenser to warn consumers of potential risks, and any consumer claim for consequent damages is legally against only the final and retail supplier.

So no supplier of black cohosh is protected against consequent liability unless he gets a signed waiver from the purchaser after the recorded warning about its potential toxicity.

16 June 2010

there are no new adverse toxicity reports on Hebalife, black cohosh or kava so far in 2010 .

Both Herbalife, and black cohosh products, remain marketed and in demand in South SAfrica.

There are no new serious adverse reports or concerns published on Pubmed or Google about Herbalife products in 2009.

On Pubmed there were 2 new cases of liver and coagulation problems associated with black cohosh in mid2009, from a Germanic and an Italian institute; and 14 hepatitis cases associated with kava ingestion confirmed from around the world .

4 Jan 2009

This review is not about benefit of black cohosh (independent trials show none for menopause symptoms) or Herbalife (trials support that Herbalife is indeed a weight loss aid), or kava (it is a confirmed anxiolytic analgesic euphoriant); but about toxicity potential however rare – considering that none of these products can make any claim to being a necessity.

Contamination aside, there are no new relevant reports on Herbalife the past two months on Pubmed,

but indeed 4 new reports on black cohosh; and one on kava.

Lessons for black cohosh and Herbalife may be learnt from kava. Kava-kava was hastily banned eg in Europe and South Africa early this decade owing to reputed association with hepatotoxic deaths. But on careful study these toxicity claims appear to be uncertain.

The claimed benefits of kava are analgesic, euphoriant and relaxant, without addiction potential. The four trials of Kava (between 1991 and 2003, in Italy and Germany) confirmed that kava has anxiolytic benefits in the menopause syndrome.) . The hepatotoxicity (not reported from the source – Polynesia – unless taken by alcoholics) was reported largely from western countries, where commercially sold kava extract was apparently differently extracted, and from the aerial leftovers of the kava; whereas in Polynesia it is extracted only from the root. A recent website from the NIH shows it is not banned there, but expresses much caution.

A careful analysis of kava hepatotoxicity by Teschke ea in Germany last month again finds little evidence of toxicity if kava is taken from a reputable manufacturer at prescribed dose and for short duration – as applies equally to alcohol, and most drugs.

Herbalife

An objective NICUS Nutritional Institute of University of Stellenbosch Report critical of Herbalife is quoted verbatim in the Summer 2008 Newsletter of the Association of Dieticians of SA. NICUS- a world authority in Nutrition – confirms it stands by this report. It could thus be taken as a directive (to condemn Herbalife)- to dieticians for whose professional advice some patients wrongly substitute diet supplements; where these modalities- careful professional diet advice and counselling, and supplements- are actually complementary..

But there does not appear to be any more evidence to condemn Herbalife than there was a year ago. As far as Pubmed and Google reveals, the reports [to date end of 2008 on Pubmed) of adverse effects were from 4 discrete European regions [ Iceland; Switzerland; Spain & Israel) , apparently wth locally formulated Herbalife, not the USA main factory product, leading to assumption of a local production fault. There appear to have been 2 cases of liver failure in some 33 affected patients, in one of whom liver transplant became necessary but the patient died.. .

One cannot condemn all babyfood because some is deliberately adulterated with melamine by ruthless Chinese sham factories. Commercial babyfood is arguably a necessity for many.

We await an updated rebuttal from Herbalife in the new year- but there does not seem to be anything for them to add to their rebuttal of last year..There has been no published evidence to justify update on Herbalife during 2008.

The accusation (by one patient, and a convicted fraudster, Minkow) of a claimed lead-contaminated Herbalife batch in California has, strangely, generated no updates for months now- but on the wiki herbalife update , it says “In August 2008, Minkow retracted all accusations against Herbalife and removed any mention of the company from his Web site.[30]” – there is no report of whether Herbalife bought his silence or not , which is a pity- see also. ; but see also heavy flak against Minkow , suggesting that his whole campaign was a successful bear scam to profit from Herbalife shares.

The current Wiki Herbalife review also quotes a new trial validating benefit for weightloss. Caveat Emptor.

It may be asked why a Nutritional authority like NICUS: warns against Herbalife but not against the potentially fatal black cohosh. New independent analyses are both for and against them:

ie

Black Cohosh:

Analyses of case reports from Univ Florida (Palacio 2009) and Italy (Borrelli 2008) recommend caution about black cohosh for humans in view of adverse case reports; while a German analysis (Teschke 2008) exonerates black cohosh in every single case till then.

A trial from USA (Davis 2008) found that “black cohosh significantly increased the incidence of lung metastases in tumor-bearing mice compared with mice fed the isoflavone-free control diet”.

Clearly the valid divergence of opinion comes down to complex statistics of probability.

Black cohosh has been associated with severe liver failure and transplantation in a number of women on a number of continents, for which reason the local Health Products Association, like all responsible authorities , finally agreed and issued recommendations that Black Cohosh label must be black-boxed- there is no justification for it’s sale as a useful product, unlike the role than can be argued for food substitute powders.

This review is not about benefit, but safety. Regulators remain silent about drastically curtailing sale of the most lethal substances in widespread unregulated (and unnecessary) use- paracetamol, other nonsteroidal anti-inflammatories, statins for uncomplicated mild-to-moderate lipidemia, alcohol, tobacco and sugar, and pollution of everything by industrial adulteration with synthetic (often estrogenic) endocrine disruptors and virtually all fast foods with cornstarch and/or sugar.

The hysterical approval of diethylstilbestrol DES by the FDA by 1950, and for a massive 1950 maternity trial against all evidence (even though it’s toxicity was recognized by 1953, it’s sale anywhaere was finally banned only 20 years later) continues to torment the original myriads of guineapig women, their children and now grandchildren. These scandals are dictated by individual opportunist, corporate and governmental greed, and indifference to medical evidence and prevention.

The analogy for black cohosh, kava and Herbalife is perhaps:

#the ~20year delays before the FDA would licence the lifesaving lithium salt, and metformin, in USA;

#the ~5year hysteria over HRT after the Women’s Health Initiative – when the over-estimated risks of inapproriate use of OHT in elderly women were stupidly and harmfully (for thousands of women) extrapolated to young women and other HRT preparations;

and

#the melamine- baby milk formula catastrophe – the problem for the latter was exclusively some contaminated babyfood batches made in China especially for the lucrative export market. .

The jury can thus be considered as still out on both black cohosh, kava and Herbalife, until manufacturers of commercial products (not traditional preparations of eg kava and black cohosh taken by residents who grow these) can produce evidence, confirm that the risk was limited to specific batches of the commercial product and adherence to accepted recommendations, and not due to other possible risk factors.

LIVER DAMAGE IN EUROPE ASSOCIATED WITH HERBALIFE USE:

4 Sept 2007 Review
The following reports below of HerbaLife-associated liver failure appear on Medline – from Spain, then Israel and Switzerland.
:The July 2007 reports of the two dozen Herbalife-associated hepatitis cases from Israel & Switzerland reveal that liver problems occurred after about 5 months on the products; and that relapse occurred in about 20% on rechallenge with Herbalife ie in this percentage the association is proven.

Herbalife results for weight control have been reported as good. The only problem is historical according to the current Wikipedia entry: “Some of the original Herbalife weight loss products contained the active ingredient Ma Huang or Sida cordifolia, two herbs containing ephedrine alkaloids.

Adverse reactions involving the company’s Thermojetics original green tablets were recorded by the U.S. Food and Drug Administration and Herbalife subsequently stopped using ephedrine in its products in the face of rising insurance premiums.[3][4] The U.S. FDA banned supplements containing ephedra in 2004.[5]“

It is possible that the case reports below are unrelated to Herbalife itself , or that in those countries ephedra-containing Herbalife was still in use at the time, or that potentially hazardous herbs etc were added locally.

A score of drugs and herbs can cause liver damage, topical ones – albeit rarely- include mushrooms; black cohosh and kava – see a recent list.

Drugs like ticrynafen, methyldopa and cerivastatin were discarded among other reasons because of liver problems, which are among many reasons why necessary sex hormone contraception and replacement should rather not use designer patent ie synthetic drugs, and especially not by mouth (hepatic first pass effect).

So it is always difficult to blame a single product, as the ongoing debate about black cohosh shows – which many “first world” regulators have “black boxed” ie added a compulsory warning to black cohosh warnings.

As with black cohosh, with a rare adverse event report, users of such products must weigh up for themselves.

As they say, since Herbalife tends to be custom-made in each country, with numerous ingredients (some undisclosed), it is so far impossible to incriminate whether the cause was local product corruption, or some appreoved component, of which the known possible culprits are ephedra and camelia.

Other known hepatotoxic herbs like black cohosh, kava and mushrooms were not mentioned. A few of the patients had viral hepatitis. Only 7 cases had also taken other known potential liver sensitizers – some synthetic sex hormones (4), aspirin (3), statin (1) and hydrochlorothiazide(1), of which 2 cases had positive recurrence of hepatitis on rechallenge with Herbalife.

UCT Medicines Information Centre is unaware of any such problems locally, and can recollect only perhaps 2 queries about Herbalife in some 23 years. Clarification is awaited from Herbalife headquarters.

From Swiss data the estimated incidence was below 2 cases per million Herbalife users, but both studies were based only on hospital records.

Considering the severe global problem of hepatitis from other causes (due to alcohol; obesity/diabetes (steatohepatitis, sulphonylureas, glitazones); numerous infections; carbon tetrachloride; synthetic sex hormones (oral contraception and postmenopausal hormone therapy) , mushrooms, antibiotics and antivirals, , autoimmune disease, antiepileptics, nifedipine, amitryptiline, allopurinol, nonsteroidal anti-inflammatories including aspirin and paracetamol , black cohosh, kava, antifungals and paracetamol), and that the rare adverse association of herbalife with liver damage may well have been limited only to Herbalife products made in those three “European” countries at that time, there is clearly no cause for alarm about Herbalife – just awareness.

The centuries-proven plant galega officinalis (extract) metformin after 85years of modern use remains the only drug proven in longterm use to both reduce liver damage, lipidemia, thrombosis, adiposity and insulin resistance, and thus almost halve the incidence of new diabetes, hypertension/vascular disease, cancer and thus all-cause premature medical mortality.

In defence of free market enterprise and choices, those who choose convenience safe proven food substitutes or other complementary products as part of an acceptable balanced regime advocated by suppliers like Herbalife do well, they should just be sure of the ingredients and supplier; and they should report and discuss what they use with some knowledgable up-to-date healthcare provider.

ResponsefromHerbalife

04.09.07Herbalife’s South Africa CEO responds reassuringly:

Good day,
Herewith a statement from Herbalife in response to the issues raised by yourself earlier in the week:

While we are aware of reports of abnormal liver function blood tests such as those reported by Dr. Oneta, our extensive consultation with internationally recognised liver experts has led repeatedly to the conclusion that these associations in time cannot be linked to any Herbalife product.

These small numbers of reports are anecdotal and millions of satisfied customers all over the world have been using our products for more than 27 years. All Herbalife products are formulated and manufactured in accordance with strict standards overseen by the Herbalife Scientific Advisory Board, which is chaired by David Heber, M.D., Ph.D., F.A.C.P., F.A.C.N. Quality control is overseen by our Scientific Affairs Group, chaired by Y. Steve Henig PhD and made up of an international panel of experts in nutrition and botanical dietary supplements.

Herbalife products, which are now sold in 65 countries, are formulated, registered and labelled in accordance with the regulatory requirements in every market where sold. All Herbalife products are safe to consume as directed.

Many consumers who choose to use Herbalife weight-management products for weight loss are overweight, some significantly so. Pre-existing medical conditions such as obesity and diabetes can be associated with non-alcoholic fatty liver disease, a disorder that may return certain types of abnormal blood test results. These test results, therefore, may have nothing to do with any herbal supplement, but rather are the result of a pre-existing medical condition. In addition, it is possible for an individual to have an allergic reaction to our products, the same way one might to any food product; for example, strawberries or shellfish. Herbalife supports the recommendation that consumers visiting their doctors for medical treatment inform them of any supplements they may be taking.

As a socially responsible company, we operate an adverse event reporting procedure that deals with the small number of queries we have from doctors and consumers and we operate an open dialogue policy with the medical community. All adverse event reports are investigated thoroughly in consultation with the consumer and the physician (if they are available) to fully understand the facts. None have resulted in the compulsory withdrawal of any product, ever. In the United States, Herbalife actively lobbied Congress to pass legislation mandating the submission of all dietary supplement and over-the-counter drug serious adverse events to the Food & Drug Administration. That new law takes effect December 22, 2007.”

REFS:

J Hepatol. 2007 Oct;47(4):521-526. Herbal does not mean innocuous: Ten cases of severe hepatotoxicity associated with dietary supplements from Herbalife((R)) products. Schoepfer AM, ea.University Hospital Bern, Switzerland.
METHODS: To determine the prevalence and outcome of hepatotoxicity due to Herbalife((R)) products. A questionnaire was sent to all public Swiss hospitals. Reported cases were subjected to causality assessment using the CIOMS criteria. RESULTS: Twelve cases of toxic hepatitis implicating Herbalife((R)) preparations (1998-2004) were retrieved, 10 sufficiently documented to permit causality analysis. Median age of patients was 51 years (range 30-69) and latency to onset was 5 months (0.5-144). Liver biopsy (7/10) showed hepatic necrosis, marked lymphocytic/eosinophilic infiltration and cholestasis in five patients. One patient with fulminant liver failure was successfully transplanted; the explant showed giant cell hepatitis. Causality assessment of adverse drug reaction was classified as certain in two, probable in seven and possible in one case(s), respectively. CONCLUSIONS: We present a case series of toxic hepatitis implicating Herbalife((R)) products. Liver toxicity may be severe. A more detailed declaration of components and pro-active role of regulatory agencies would be desirable.

J Hepatol. 2007 Oct;47(4):514-520. Association between consumption of Herbalife((R)) nutritional supplements and acute hepatotoxicity. Elinav E, ea -Hebrew University Medical Center, Israel.
: In 2004, identification of four index cases of acute hepatitis associated with Herbalife((R)) intake led to a ministry of health investigation in all Israeli hospitals. Twelve patients with acute idiopathic liver injury in association with consumption of Herbalife((R)) products were investigated.
RESULTS: Eleven of the patients were females, aged 49.5+/-13.4 y. One patient had stage I primary biliary cirrhosis and another had hepatitis B. Acute liver injury was diagnosed after 11.9+/-11.1 months of initiation of Herbalife((R)) consumption. Liver biopsies demonstrated active hepatitis, portal inflammation rich with eosinophils, ductular reaction and parenchymal inflammation with peri-central accentuation.
. CONCLUSIONS: An association between intake of Herbalife((R)) products and acute hepatitis was identified in Israel. We call for prospective evaluation of Herbalife((R)) products for possible hepatotoxicity.

Accompanying his 32year old partner (with like her mother BRCA+ breast cancer ), a young man this week complains sorrowfully of total erectile failure within three days every time he resumes fluoxetine for longstanding depression.

This may suit those patients who eschew sexuality, who knowingly choose chemical castration.. But the drug doesnt fix the causes of depression, merely palliates, often no better than a placebo, sometimes worse- compared to natural multibeneficial antidepressant supplements.

We already long live in a sea of estrogenic endocrine disruptors decimating many species including humans, like pesticides and PCBs, as so aptly described by Deborah Cadbury and Prof Nils Skakkebaek in classic books eg The Feminization of Nature and The Estrogen Effect.

Endocrine disruption studies of antidepressants (eg fluoxetine Prozacs, mianserin Lantanon (its commercial analogue successor is now Remeron), Bupropion Wellbutrin Zyban; Venlafaxine Effexor and desimipramine) in surface water in Canada, USA, Mexico, Brazil and Belgium since 2006, and longer for antipsychotics, statins and NSAIDS, show estrogenic ie antiandrogenic risks for eg gender development and thus for breast/prostate cancer, for virility and fertility..

Doctors mostly blithely ignore that reproductive young females have by evolutionary reproductive necessity 100fold lower androgenic:estrogenic balance (eg 3:1) than men (eg 300:1), and are also far more prone than males both to estrogenic contraception prescription harm, and to common major depression and autoimmune disease like rheumatod arthritis and lupus, and thus to the double peril of mutiple estrogenic prescription.

Recently common NSAIDs eg ibrufen, diclofenac and mefanemic acid have been shown to be estrogenic in fish.

But such elective prescription of ( endocrine disruption) cancer- and infertility- promotors (antidepressants, NSAIDS, hormone contraception and HRT etc) , is hardly desirable or ethical at any age, especially when patients and their parents are not informed of the grave risks of these drugs with no proven longterm benefits (except for contraception).

and into the gross dangerous overprescription of diabetogenic depressing hepato-nephro-myotoxic statins for all.

Popular painkillers eg opioids like oxycodin, fentanyl, tramadol on the other hand are similarly also powerful longacting hypoandrogenism–inducing drugs promoting estrogen dominance – which further complicates the misery and depression of those in chronic pain or depression, including from cancer, especially in women as well as men; who thus require monitoring of gonadal hormone levels and, if deficient, testosterone replacement. Aloisi ea Univ Siena 2012.

ndb

Reprod Toxicol. 2012:34:80-5. In vivo and in vitro estrogenic activity of the antidepressant fluoxetine.Müller JC, Imazaki PH, Boareto AC, Lourenço EL, Golin M, Vechi MF, Lombardi NF, Minatovicz BC, Scippo ML, Martino-Andrade AJ, Dalsenter PR. University of Paraná, Brazil. .Recent years have seen an increase in the use of antidepressant drugs, especially fluoxetine (FLX), in sensitive populations, such as pregnant and lactating women. Although some evidence suggests a possible endocrine action of FLX, no specific studies have been performed to investigate this hypothesis. In the present study, we investigated the possible (anti)androgenic and (anti)estrogenic actions of FLX using Hershberger, uterotrophic (0.4, 1.7, and 17mg/kg), and reporter gene (7.6-129μM) assays. In the Hershberger assay, no differences were observed in androgen-dependent organ weights. However, the uterotrophic and gene reporter assays indicated a possible estrogenic action of FLX. Uterine weight increased in the 1.7 and 17mg/kg/day groups in the 3-day uterotrophic assay in immature rats. Additionally, noncytotoxic concentrations of FLX induced estrogenic responses and increased the estrogenic response of estradiol in MCF-7 breast cancer. Recent years have seen an increase in the use of antidepressant drugs, especially fluoxetine (FLX), in sensitive populations, such as pregnant and lactating women. Although some evidence suggests a possible endocrine action of FLX, no specific studies have been performed to investigate this hypothesis. In the present study, we investigated the possible (anti)androgenic and (anti)estrogenic actions of FLX using Hershberger, uterotrophic (0.4, 1.7, and 17mg/kg), and reporter gene (7.6-129μM) assays. In the Hershberger assay, no differences were observed in androgen-dependent organ weights. However, the uterotrophic and gene reporter assays indicated a possible estrogenic action of FLX. Uterine weight increased in the 1.7 and 17mg/kg/day groups in the 3-day uterotrophic assay in immature rats. Additionally, noncytotoxic concentrations of FLX induced estrogenic responses and increased the estrogenic response of estradiol in MCF-7 breast cancer cells transfected with luciferase.

Pharmacol Biochem Behav. 2013103: 659-65..Participation of estrogen receptors in the antidepressant-like effect of prolame on the forced swimming test. Lemini C, Cruz-López B, Martínez-Mota L Universidad Nacional Autónoma de México, Mexico.Estrogen therapy may produce antidepressant-like actions, but the side effects, such as thromboembolic events, may restrict its use among women. The 17β-aminoestrogens (AEs) [prolame [17β-(3-hidroxy-1-propylamino)-1,3,5(10)-estratrien-3-ol)], butolame [17β-(3-hidroxy-1-butylamino)-1,3,5(10)-estratrien-3-ol)], and pentolame [17β-(5-hidroxy-1-pentylamino)-1,3,5(10)-estratrien-3-ol)] induce estrogenic and anticoagulant actions, effects that could prove advantageous in an estrogen therapy; however, their antidepressant-like effects have not been described. The objective of this study was to determine the effect of these 17β-AEs (prolame, butolame and pentolame) in the forced swimming test (FST), an animal model sensitive to antidepressant drugs, and to establish the role of estrogen receptors in such actions. Ovariectomized female rats treated with prolame (10-200 μg/rat) showed a reduction in immobility and an increase in active behaviors in the FST, while this effect was not produced by butolame and pentolame (10-200 μg/rat). The antidepressant-like effect of prolame was similar to that of 17β-estradiol (E2, 5-20 μg/rat), sharing with it a biphasic profile but at higher doses. Antidepressant-like actions of prolame and E2 were not associated with changes in locomotor activity. With respect to a control group tamoxifen (15 mg/kg) by itself produced no changes in all behavioral evaluations, but canceled the antidepressant-like effect of prolame and E2. It is concluded that estrogen receptors participate in antidepressant-like effect of both estrogens in the FST. Antidepressant-like activity of different AEs is discussed considering their differences in chemical structure and the schedule used. Our results show additional central actions of prolame besides its pro-sexual, anti-coagulant, estrogenic and anxiolytic activity.

Aquat Toxicol. 2011:104::38-47. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows. Schultz MM, Painter MM, Bartell SE, Logue A, Furlong ET, Werner SL, Schoenfuss HL The College of Wooster, OH USA Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimephales promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish–a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies.

Pharmacol Biochem Behav. 2008 ;88:332-40.Estrogens participate in the antidepressant-like effect of desipramine and fluoxetine in male rats.Martínez-Mota L, Cruz-Martínez JJ, Márquez-Baltazar S, Fernández-Guasti A Instituto Nacional de Psiquiatría Mexico City In male rats, the antidepressant-like effect of fluoxetine (FLX) and desipramine (DMI) in the forced swimming test (FST) is reduced by orchidectomy and partially restored by testosterone (T). It is unknown if this modulation of T is produced by its estrogenic metabolites. The objectives of this study were to evaluate if the aromatase inhibitor, formestane, interferes with the antidepressant-like effect of DMI and FLX in intact male rats, and to analyze if 17beta-estradiol (E2) modifies the FST and interacts with the antidepressants in orchidectomized (Orx) males. Intact males received DMI (1.25-5.0 mg/kg) and FLX (2.5-10 mg/kg) alone or in combination with formestane (17.5 mg/kg). Orx rats received E2 (5, 10, 20 and 40 microg/rat) or the combination of E2 [at sub-threshold (5 microg/rat) and optimal (10 microg/rat) doses] plus sub-effective doses of DMI (2.5 mg/kg) or FLX (10 mg/kg). Serum testosterone and estradiol levels were measured in intact-control and -formestane treated animals as well as in castrated males replaced with various doses of E2. Formestane in intact males lacked of an action in the FST, but cancelled the antidepressant-like effect of DMI and FLX. E2 at the supra-physiological doses of 10 and 20 microg/rat produced antidepressant-like effects. E2 at 5 microg/rat (that re-established the levels of this hormone to physiological levels) and at 10 microg/rat restored the antidepressant-like action of DMI and FLX in Orx rats. It was concluded that estrogens participate in the antidepressant-like effect of DMI and FLX in the FST.

Chemosphere. 2006:;65:1836-45.. Effects of the antidepressant mianserin in zebrafish: molecular markers of endocrine disruption.van der Ven K, Keil D, Moens LN, Hummelen PV, van Remortel P, Maras M, De Coen W. University of Antwerp, Belgium. Due to their environmental occurrence and intrinsic biological activity, human pharmaceuticals have received increasing attention from environmental and health agencies. Of particular, ecotoxicological concern are drugs that affect nervous- and endocrine-systems. Zebrafish genome-wide oligo arrays are used to collect mechanistic information on mianserin-induced changes in gene expression in zebrafish. Gene expression analysis in brain and gonad tissue clearly demonstrated the estrogenic activity of mianserin and its potency to disrupt normal endocrine (estrogenic) signaling, based on induction of molecular biomarkers of estrogenicity (e.g., vitellogenin1 and zona pellucida proteins). The possible mechanism underlying this estrogenic activity of mianserin is disturbance of the Hypothalamo-Pituitary-Gonadal (HPG) axis by direct interference of mianserin with the serotonergic and adrenergic systems in the brain of zebrafish. Taking into account the importance of the HPG-axis, and considering the concept of ‘critical window of exposure’, our results reveal the importance for more elaborate testing of endocrine disruptive effects of aquatic antidepressants at different lifestages and during longer exposure periods (e.g., life cycle studies). Although there is a low concordance between the gene expression results in this study and previous cDNA microarray hybridizations, the global mechanistic expression patterns are similar in both platforms. This argues in favor of pathway-driven analysis of gene expression results compared to gene-per-gene analysis.

J Hazard Mater. 2013 Jun 15;254-255:242-51. .Effects of non-steroidal anti-inflammatory drugs on hormones and genes of the hypothalamic-pituitary-gonad axis, and reproduction of zebrafish. Ji K, Liu X, Lee S, Kang S, Kho Y, Giesy JP, Choi K. Seoul National University, Korea.This study was conducted in two experiments, to identify non-steroidal anti-inflammatory drugs (NSAIDs) with high endocrine disruption potentials, and to understand consequences of exposure to such NSAIDs in fish. In the first experiment, the effects of five NSAIDs on hormones and gene transcriptions of the hypothalamic-pituitary-gonad (HPG) axis were evaluated after 14 d exposure of adult zebrafish. Ibuprofen and mefenamic acids were identified to increase the concentrations of 17β-estradiol and testosterone in females significantly, while decreased those of testosterone among male fish. Significant up-regulation of fshβ, lhβ, fshr and lhr were observed in females, whereas down-regulation was observed in males exposed to each NSAID. In the second experiment, ibuprofen was chosen as a model chemical. Adult zebrafish pairs were exposed to ibuprofen for 21 d, and the effects on reproduction and development of offspring were examined. The egg production was significantly decreased at ≥1 μg/L ibuprofen, and parental exposure resulted in delayed hatching even when they were transferred to clean water for hatching. The results demonstrated that ibuprofen could modulate hormone production and related gene transcription of the HPG axis in a sex-dependent way, which could cause adverse effects on reproduction and the development of offspring.

University of Algarve, Portugal .buprofen (IBU) is one of the most sold over-the-counter non-steroidal anti-inflammatory drugs (NSAID) and widely detected in the aquatic ecosystems. Nevertheless, the information regarding IBU effects in biota is still sparse. The goal of this study was to assess IBU potential effect as oxidative stress and endocrine disruption inducer in mussel Mytilus galloprovincialis applying a battery of biomarkers. Over two weeks of exposure to IBU (250 ngL(-1)), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), phase II glutathione S-transferase (GST) activities and lipid peroxidation (LPO) levels were determined in the digestive gland and alkali-labile phosphates (ALP) were carried out in sex-differentiated mussels’ gonads. The results confirm a transitory induction of antioxidant activities responses concomitant to lipid peroxide formation outline and an increase of ALP levels over time, particularly in exposed males which may lead to mussels’ reproductive fitness impairment highlighting a higher impact of IBU as an endocrine disruptor than as a short-term reactive oxygen species (ROS)-generator.

Aquat Toxicol. 2011 ;105:264-9..Non-steroidal anti-inflammatory drug (NSAID) ibuprofen distresses antioxidant defense system in mussel Mytilus galloprovincialis gills.Gonzalez-Rey M, Bebianno M University of Algarve, Portugal.Active pharmaceutical ingredients (APIs) are presently considered an emergent class of environmental contaminants. Ibuprofen (IBU) is one of the most applied non-steroidal anti-inflammatory drugs (NSAIDs) in the world. Several authors report the occurrence of IBU in influents and effluents of waste water treatment plants (WWTPs), surface, river and public tap water in numerous countries. However, very little is known about the risks and chronic effects of IBU exposure in non-target organisms. This approach undertakes the assessment of several oxidative stress biomarkers responses through the analysis of antioxidant enzymes activities (superoxide dismutase – SOD, catalase – CAT, glutathione S-transferase – GST, glutathione reductase – GR) and lipid peroxidation (LPO) levels in sentinel species mussel Mytilus galloprovincialis gills exposed for 2 weeks to an environmental realistic concentration of IBU. Results clearly show the significant induction and positive correlation between SOD activity and LPO in exposed gills, concomitant to an antioxidant defense depletion of CAT, GR and GST compared to controls. The integration of all biomarkers in mussels’ gills separates non- and exposed groups supporting the breakdown of the redox defense system and IBU’s pro-oxidant action. Further studies are needed to test possible endocrine disruption effects in mussels’ reproduction fitness as IBU is involved on prostaglandins biosynthesis inhibition.

BMC Med. 2013; 11:57.. The effect of statins on testosterone in men and women, a systematic review and meta-analysis of randomized controlled trials. Schooling CM, Au Yeung SL, Freeman G, Cowling BJ. CUNY School of Public Health York, .Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates more than other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statins unexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would be expected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins’ pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone. METHODS:A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, Medline and ISI Web of Science databases until the end of 2011, using ‘(Testosterone OR androgen) AND (CS-514 OR statin OR simvastatin OR atorvastatin OR fluvastatin OR lovastatin OR rosuvastatin OR pravastatin)’ restricted to randomized controlled trials in English, supplemented by a bibliographic search. We included studies with durations of 2+ weeks reporting changes in testosterone. Two reviewers independently searched, selected and assessed study quality. Two statisticians independently abstracted and analyzed data, using random or fixed effects models, as appropriate, with inverse variance weighting.RESULTS:Of the 29 studies identified 11 were eligible. In 5 homogenous trials of 501 men, mainly middle aged with hypercholesterolemia, statins lowered testosterone by -0.66 nmol/l (95% confidence interval (CI) -0.14 to -1.18). In 6 heterogeneous trials of 368 young women with polycystic ovary syndrome, statins lowered testosterone by -0.40 nmol/l (95% CI -0.05 to -0.75). Overall statins lowered testosterone by -0.44 nmol/l (95% CI -0.75 to -0.13). CONCLUSIONS: Statins may partially operate by lowering testosterone. Whether this is a detrimental side effect or mode of action warrants investigation given the potential implications for drug development and prevention of non-communicable chronic diseases. See commentary article here http://www.biomedcentral.com/1741-7015/11/58.

Chemosphere. 2009 ;77 :1285-91.Occurrence and fate of rosuvastatin, rosuvastatin lactone, and atorvastatin in Canadian sewage and surface water samples. Lee HB, Peart TE, Svoboda ML, Backus S. Aquatic Ecosystem Protection Research Branch, Environment Canada Rosuvastatin (RST) and atorvastatin (ATO) are prescription drugs and members in the statin family used for the treatment of elevated cholesterol levels. A method using solid-phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of ATO, RST and its metabolite rosuvastatin lactone (RSTL) in sewage and surface water samples has been developed. In the influent and effluent samples collected from 11 sewage treatment plants located in Ontario, Canada, ATO, RST, and RSTL were detected in all samples with median concentrations of 166 ng L(-1) (influent) and 77 ng L(-1) (effluent) for ATO, 448 ng L(-1) (influent) and 324 ng L(-1) (effluent) for RST, as well as 158 ng L(-1) (influent) and 41 ng L(-1) (effluent) for RSTL. Due to the inter-conversion between RST and RSTL, the total concentration of RST and RSTL in a sewage sample should be reported. The median removal rate by wastewater treatment was 66% for ATO and 22% for RST and RSTL combined. These statins were quite persistent in sewage. After a storage period of 21 and 62 days, there was only a slight decrease in ATO concentration and no change in the total RST concentrations. These three compounds were also detected in a number of surface water samples at low ng L(-1) concentrations. This is the first reported occurrence and fate of RST and RSTL in the Canadian aquatic environment.

Consequences of long-term exposure to diclofenac up to 3 months were evaluated using freshwater crustaceans (Daphnia magna and Moina macrocopa) and a fish (Oryzias latipes). Marked decrease of reproduction was observed at 25 mg/L for D. magna, and at 50 mg/L for M. macrocopa. Three-month exposure of fish to 0.001-10 mg/L of diclofenac resulted in significant decreasing trend in hatching success and delay in hatch. The hatching of the eggs produced from the fish exposed to 10 mg/L was completely interfered, while fertility of the parent generation was not affected. Gonadosomatic index (GSI) of female fish was also affected at 10 mg/L. Predicted no effect concentration of diclofenac was estimated at 0.1 mg/L, which is a few orders of magnitude greater than those observed in ambient water. Therefore direct impact of diclofenac exposure is not expected. However its bioaccumulation potential through food web should warrant further evaluation.\

J Toxicol Environ Health A. 2009;72(10):633-41. Life-cycle exposure of fathead minnows to a mixture of six common pharmaceuticals and triclosan.Parrott JL, Bennie DT Water Science and Technology Directorate, Environment Canada,Fathead minnows were exposed for a life cycle to environmentally relevant concentrations of a mixture of six common pharmaceuticals and one personal care product (nominal concentrations: 1,000, 300, 100, 30, or 10 ng/L). Mean measured concentrations of each chemical in the highest fish exposure aquaria were: naproxen 793 ng/L, gemfibrozil 662 ng/L, diclofenac 331 ng/L, ibuprophen 217 ng/L, triclosan 115 ng/L, salicylic acid 67 ng/L, and acetaminophen (chemical analysis inconclusive, nominal 1000 ng/L). Fish exposed for a life cycle even to the highest concentrations of the six pharmaceuticals and personal care product (PPCP) mixture showed no significant changes in growth and development compared to control. Length, weights, condition factors, liver weights, and gonad weights of PPCP-exposed fish were similar to water and solvent controls (0.000005% ethanol v/v). There were no marked effects of PPCP mixture exposure on external sex characteristics of the fish or on egg production. The only parameter that appeared to be affected was percent larval deformities in F1, which showed a significant increase in the 100- and 300-ng/L (nominal) PPCP mixture. Larvae from control fish had 4.7% (water controls) and 3.4% (solvent controls) deformities, compared to 9.3% in the 100-ng/L (nominal) PPCP mixture and 9.2% deformities in the 300-ng/L (nominal) PPCP mixture. Chronic exposure to environmentally relevant concentrations of seven PPCP most often detected in Canadian municipal wastewater effluents (MWWE) did not appear to affect fathead minnow survival, growth, or egg production, although it produced quantitative increases in deformities in the F1 generation.

Hum Reprod. 1993 Aug;8(8):1168-72.Autonomic nervous modulation and effects of a prostaglandin synthase inhibitor on human cervical secretion.Jonsson B, Hammarström Karolinska Hospital, Stockholm, Sweden.Modulation of cervical secretion at ovulation time was studied in 10 women with regular menstruations. In an in-vivo model with repeated collection of mucus samples during three 90-min periods, the amounts of mucus in a control cycle and in three experimental cycles were compared. Drugs interacting with the autonomic nervous system and a prostaglandin synthase inhibitor were administered at time of ovulation. The cholinomimetic drug carbacholine significantly increased cervical secretion, while the anticholinergic drug butylscopolamine markedly inhibited this secretion. A long-lasting decrease in secretion was seen after administration of the prostaglandin synthase inhibitor diclofenac. Beside regulation of cervical secretion by the ovarian hormones, these results suggest an autonomic nervous modulation of cervical secretion, and in addition an impact on cervical by a prostaglandin synthase inhibitor. The effects on fertility regulation in the female are discussed.

Water Res. 2010 Jan;44(2):555-66. Oxidative transformation of micropollutants during municipal wastewater treatment: comparison of kinetic aspects of selective (chlorine, chlorine dioxide, ferrate VI, and ozone) and non-selective oxidants (hydroxyl radical).Lee Y, von Gunten U. Federal Institute of Aquatic Science and Technology, Duebendorf, Switzerland. Chemical oxidation processes have been widely applied to water treatment and may serve as a tool to minimize the release of micropollutants (e.g. pharmaceuticals and endocrine disruptors) from municipal wastewater effluents into the aquatic environment. The potential of several oxidants for the transformation of selected micropollutants such as atenolol, carbamazepine, 17 alpha-ethinylestradiol (EE2), ibuprofen, and sulfamethoxazole was assessed and compared. The oxidants include chlorine, chlorine dioxide, ferrate(VI), and ozone as selective oxidants versus hydroxyl radicals as non-selective oxidant. Second-order rate constants (k) for the reaction of each oxidant show that the selective oxidants react only with some electron-rich organic moieties (ERMs), such as phenols, anilines, olefins, and deprotonated-amines. In contrast, hydroxyl radicals show a nearly diffusion-controlled reactivity with almost all organic moieties (k>or=10(9)M(-1) s(-1)). Due to a competition for oxidants between a target micropollutant and wastewater matrix (i.e. effluent organic matter, EfOM), a higher reaction rate with a target micropollutant does not necessarily translate into more efficient transformation. For example, transformation efficiencies of EE2, a phenolic micropollutant, in a selected wastewater effluent at pH 8 varied only within a factor of 7 among the selective oxidants, even though the corresponding k for the reaction of each selective oxidant with EE2 varied over four orders of magnitude. In addition, for the selective oxidants, the competition disappears rapidly after the ERMs present in EfOM are consumed. In contrast, for hydroxyl radicals, the competition remains practically the same during the entire oxidation. Therefore, for a given oxidant dose, the selective oxidants were more efficient than hydroxyl radicals for transforming ERMs-containing micropollutants, while hydroxyl radicals are capable of transforming micropollutants even without ERMs. Besides EfOM, ammonia, nitrite, and bromide were found to affect the micropollutant transformation efficiency during chlorine or ozone treatment.

Toxicol Appl Pharmacol. 2007 Dec 1;225:142-53. .Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds.Gracia T, Hilscherova K, Jones PD, Newsted JL, Higley EB, Zhang X, Hecker M, Murphy MB, Yu RM, Lam PK, Wu RS, Giesy JP.Michigan State University, The H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3betaHSD2, CYP11beta1, CYP11beta2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11beta2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11beta2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The beta-agonist salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different.

A Specialist Family Internist Clinic offers consultations by appointment especially for managing (and ideally preventing) the major chronic degenerative diseases of aging and maintaining physical, mental (and why not sexual?) vigour to a ripe and healthy old age; as well as preventing and managing acute disease at all ages.

Billing according to means ie specialist professional rates: eg as a preferred provider for Discovery Health- consultation procedure 0190; for needy patients, what the medical scheme pays Detailed medical report and advice protocol provided at R300. Even Hospital Plans have to pay for outpatient consultation for scores of PMBs ie Prescribed Medical benefit conditions like Menopause.

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